JU 


Columbia  ?Hniber$itp 
in  tfje  Cttp  of  i&to  ^orfe 

College  of  Ifihp&itwnst  anb  burgeons 


Reference  library 


RESEARCHES    ON 

RH  EU M ATIS  M 


Digitized  by  the  Internet  Archive 

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FIG.  A 

To  illustrate  Paper  No.  XXIII  upon  mitral  and  aortic  disease  of  rheumatic  origin  q>.  318). 

Fig.  A.     The  heart  of  :i  rabbit  showing  endocarditis  of  the  mitral  and  aortic  valves.     The 

heart  lias  been  greatly  enlarged  for  the  more  convenient  comparison  with  the  human  heart. 

The  vegetations  on  the  mitral  valve  are  very  extensive  and  are  in  continuity  with  equally 

extensive  ones  upon  the  aortic  cusps. 


FIG.  B 

To  illustrate  Paper  No.  XXIII  upon  mitral  and  aortic  disease  of  rheumatic  origin  (p.  318) 

Fig.  B.  A  human  heart  showing  aortic  and  mitral  endocarditis.  The  vegetations  on 
the  aortic  flap  of  the  mitral  are  in  continuity  with  extensive  vegetations  on  the  contingent 
aortic  cusp.      The  other  cusps  are  affected  in  lesser  degree.     The  mitral  valve  is  not  opened. 


[From  Quarterly  Journal  of  Medicine. 


RESEARCHES    ON 

RH  EUM  ATIS  M 


BY 

F.    J.    POYNTON 

M.D.LOND. 

Fellow  of  the  Royal  College  of  Physicians  of  London,  Vice-Dean  of  University  College 

Hospital  Medical   School,    Senior    Physician    to    Out-patients  at    University 

College  Hospital,   London,  and  at  the  Hospital  for  Sick  Children, 

Great    Ormond    Street,    Physician    in    Charge    of  the 

Children's  Ward  University  College  Hospital 

AND 

ALEXANDER    PAINE 

M.D.  (State  Medicine)  Lond.,  D.P.H.Eng. 
Director  of  the  Cancer  Hospital  Research  Institute  London 


WITH  FRONTISPIECE  IN  COLOUR 
AND  106  ILLUSTRATIONS 


NEW    YORK 
THE    MACMILLAN    COMPANY 

1914 

All  rights  reserved 


PREFACE 

We  have  collected  in  this  volume  the  chief  papers  bearing  upon 
a  research  on  the  subject  of  rheumatism  which  has  extended 
over  a  period  of  fifteen  years.  In  so  doing  we  are  well  aware 
that  few  have  the  time  to  spend  over  reading  the  details  of 
such  investigations,  but  should  the  essentials  of  this  research 
be  eventually  established,  we  feel  that  this  book  will  stand 
as  a  landmark  in  the  history  of  rheumatism  in  this  country. 
Some  of  these  papers  were  written  before  we  demonstrated 
what  we  believe  to  be  the  exciting  cause  of  the  disease  ;  others 
elucidate  the  nature  and  action  of  that  cause  ;  others,  again, 
extending  the  main  thesis,  deal  with  allied  conditions.  At 
the  conclusion  of  the  volume  the  bearing  of  these  investigations 
upon  clinical  medicine  and  public  health  is  considered  in  a 
special  article.  Owing  to  unavoidable  circumstances  we  have 
from  time  to  time  been  unable  to  collaborate,  but  others  have 
then  come  to  our  assistance.  Dr.  Vernon  Shaw,  who  had 
shown  the  identity  of  the  diplococcus  we  isolated  with  that 
described  by  Professor  Wassermann  and  Drs.  Ainley  Walker 
and  Beaton,  and  who  had  proved  the  susceptibility  of  monkeys 
to  the  infection,  assisted  us  in  a  paper  on  multiple  infections. 
Dr.  Gordon  Holmes  brought  his  deep  knowledge  of  the  patho- 
logy of  the  nervous  system  to  our  aid  in  another  upon  chorea. 
Dr.  G.  F.  Still  took  part  in  the  early  paper  upon  the  rheumatic 
nodule,  and  Dr.  D.  B.  Lees  inspired  and  collaborated  in  the 
first  paper  upon  acute  dilatation  of  the  heart.  Such  a  pro- 
longed investigation  as  this  would  have  been  impossible  without 
the  help  of  many  friends  not  only  at  St.  Mary's  and  University 
College- Hospitals  and  the  Hospital  for  Sick  Children,  Great 
Ormond  Street,  but  also  at  other  institutions.  Should  this 
work  live — and  many  of  the  recorded  facts  can  never  be  swept 
away  whatever  the  ultimate  fate  of  their  interpretations — 
we  can  truly  write  that  it  has  been  a  result  of  English  medicine, 
which  opportunity  has  called  upon  us  to  bring  to  a  focus.     We 


Vlll 


PREFACE 


recall  with  pleasure  and  gratitude  the  early  days  when  Mr. 
H.  G.  Plimmer  aided  us  in  acquiring  the  necessary  methods 
for  such  an  undertaking. 

The  illustrations  have  been  chosen  with  the  intention  of 
demonstrating  the  intimate  processes  of  rheumatism  in  the 
body,  and  for  the  purpose  of  acting  as  a  pictorial  guide  to  our 
main  conclusions.  The  kindness  of  Messrs.  Bale,  Son  and 
Daniellsson,  Messrs.  Adlard  and  Son,  the  Clarendon  Press, 
the  Lancet,  and  Medical  Press  and  Circular  has  enabled  us  to 
obtain  many  of  the  illustrations  we  thought  desirable.  All 
of  them  are  original,  and  some  have  never  been  reproduced 
before.  Our  best  thanks  are  due  to  our  artists,  Messrs.  Ford 
and  Shiells,  who  have  assisted  us  during  the  last  thirteen  years. 
We  must  also  thank  the  various  societies,  journals,  and  pub- 
lishers for  permission  to  reprint  our  papers,  due  acknowledg- 
ment  for  which  is  given  with  each  of  them. 

To  Messrs.  J.  and  A.  Churchill  we  are  indebted  for  carrying 
out  the  publication  of  this  book  in  a  manner  which  has  given 
us  much  satisfaction  and  for  the  greatest  courtesy  and  assist- 
ance. 

In  conclusion,  with  no  intention  of  appearing  to  be  presump- 
tuous, we  would  venture  to  emphasise  the  value  in  medical 
research  of  the  combination  of  the  clinician  and  bacteriologist 
working  side  by  side,  for  the  clinician  serves  to  keep  the 
bacteriologist  sane  and  the  bacteriologist  to  keep  the  clinician 
honest. 


CONTENTS 


PAGE 

INTRODUCTION  i 

PART   I 

PAPERS   WRITTEN   BEFORE   THE    ISOLATION    OF   THE 
DIPLOCOCCUS  RHEUMATICUS 

I.  Acute  Dilatation  of  the  Heart  in  the  Rheumatism  and 
Chorea  of  Childhood.  By  D.  B.  Lees,  M.D.,  and 
F.  J.  Poynton,  M.D.  13 

II.  A  Case  of  Rheumatic  Pericarditis  and  Extreme  Dila- 
tation of  the  Heart,  with  an  Investigation  into 
the  Microscopy  of  Rheumatic  Heart  Disease  44 

III.  A  Study  of  the  Heart- Wall  in  Diphtheria,  Rheumatic 

Fever,  and  Chorea  53 

IV.  Observations  upon  the  Pathology  of  the  Myocardium       63 
V.  Three  Cases  of  Fatal  Extensive  Venous  Thrombosis 

associated  with  Severe  Rheumatic  Carditis  68 

VI.  The  Histology  of  the  Rheumatic  Nodule.     By  F.  J. 

Poynton,  M.D.,  and  G.  F.  Still,  M.D.  79 

VII.  A    Case    of   Virulent    Rheumatism   with   Extensive 

Purpura  84 


PART  II 

PAPERS    WRITTEN    AFTER    THE    ISOLATION   OF   THE 
DIPLOCOCCUS  RHEUMATICUS 

SUB-GROUP  A 

VIII.  The  ^Etiology  of  Rheumatic  Fever  93 

IX.  The  Pathogenesis  of  Rheumatic  Fever  132 

X.  The  Infectivity  of  Rheumatism,  with  especial  Refer- 
ence to  Chronic  Arthritis  and  Renal  Disease  136 
ix                                                b 


CONTENTS 

PAGE 

SUB-GROUP  B 

XI.  Observations    upon    the    Arthritis    produced     in 
Rabbits  by  the  Intravenous  Inoculation  of  a  Diplo- 
coccus  isolated  from  cases  of  rheumatic  fever        141 
XII.  An  Experimental  Production  of  the  Osteo-arthritic 

Type  of  Rheumatoid  Arthritis  145 

XIII.  Observations  upon  Certain  Forms  of  Arthritis  150 


SUB-GROUP  C 

XIV.  Some  Further  Investigations  upon  Rheumatic  Fever      165 
XV.  A     Contribution     to     the     Study     of     Malignant 

Endocarditis  185 

XVI.  A  Contribution  to  the  Study  of  Rheumatic  Iritis     210 
XVII.  On  the  Relation  of  the  Staphylococcus  Pyogenes 
Aureus  to  Rheumatic  Fever.     By   F.  J.   Poynton, 
M.D.,  and  W.  Vernon  Shaw,  M.D.  214 

SUB-GROUP  D 

XVIII.  Investigations   upon    some  of  the  Nervous  Mani- 
festations of  Acute  Rheumatism  227 
XIX.  A  Contribution  to  the  Pathology  of  Chorea.     By 

F.  J.  Poynton,  M.D.,  and  Gordon  F.  Holmes,  M.D.      244 
XX.  Some  Further  Investigations  and  Observations  upon 

the  Pathology  of  Rheumatic  Fever  262 


SUB-GROUP  E 

XXI.  A  Contribution  to  the  Subject  of  Rheumatism  based 
upon  a  Study  of  Fifty-two  Cases  in  Children  under 
Five  Years  of  Age  and  an  Analysis  of  One  Hundred 
Cases  of  Fatal  Suppurative  Pericarditis  in  Child- 
hood 281 

XXII.  A  Contribution  to  the  Study  of  Rheumatism,  with 
Notes  on  the  After-Histories  of  Twenty-five 
Cases  of  "  Scarlatinal  Rheumatism  "  299 

XXIII.  A  Research  upon  Combined  Mitral  and  Aortic 
Disease  of  Rheumatic  Origin  ;  a  Contribution  to 
the  Study  of  Rheumatic  Malignant  Endocarditis      312 


CONTENTS  xi 

PAGE 

SUB-GROUP  F 

XXIV.  Arthritis  in  Association  with  Perityphlitis  359 

XXV.  The  Experimental  Production  of  Appendicitis,  by 
the  Intravenous  Inoculation  of  the  Diplococcus 
Rheumaticus  367 

XXVI.  A  Further  Contribution  to  the  Study  of  the 
^Etiology  of  Appendicitis  as  the  Result  of  a 
Blood  Infection,  with  Particular  Reference  to 
the  Tonsils  as  the  Primary  Seat  of  Infection  374 

XXVII.  Observations  upon  Appendicitis  based  upon  a 
Comparative  Study  of  the  Morbid  Anatomy  in 
the  Human  and  Experimental  Disease  378 


PART  III 

XXVIII.  A  Study  of  Acute   Rheumatism  based   upon   the 
Results  of  the  Previous  Researches 

1.  The  ^Etiology  and  Pathology  387 

2.  Symptomatology  410 

3.  Diagnosis  and  Prognosis  424. 

4.  Treatment  428 

5.  Prevention  .  433 


INTRODUCTION 

We  ask  the  reader  to  look  upon  this  collection  of  papers  as 
a  contribution  to  the  study  of  Rheumatism,  which  is  the 
result  of  an  investigation  extending  over  a  very  interesting 
period  in  the  history  of  the  disease. 

When  we  approached  the  problem  of  the  aetiology  there 
had  been  a  growing  conviction  among  many  experienced 
clinicians  that  the  acute  rheumatism  of  childhood  was  the 
result  of  an  infective  process,  but  the  evidence  other  than 
clinical,  was,  in  this  country,  meagre  in  the  extreme.  Dr. 
Mantle  in  1886  had  made  some  interesting  observations  upon 
the  bacteriology,  and  Popoff  in  Russia  had  in  1887  produced 
some  remarkable  experimental  lesions  with  a  diplococcus. 
In  France,  Triboulet  and  Apert  had  also  studied  a  diplococcus, 
and  in  Germany  Westphal,  Wassermann  and  Malkofi  had 
anticipated  some  of  our  own  results  while  our  investigations 
were  in  the  course  of  development.  It  may,  however,  be 
stated  that  in  this  country  no  pathologist  had  produced  with 
any  micro-organism  isolated  from  the  lesions  of  acute  rheu- 
matism such  results  as  endocarditis,  myocarditis,  or  peri- 
carditis, and  not  even  multiple  arthritis  was  recognised  as  a 
result  of  experimental  infection  from  rheumatic  lesions. 

It  is  difficult  to  realise  how  the  production  of  these  experi- 
mental results,  not  once,  but  repeatedly  has  influenced  English 
writings  and  altered  almost  unconsciously  the  views  that 
were  held  upon  rheumatic  processes.  Yet  who  now  would 
believe  that  the  structure  of  a  vegetation  in  rheumatic  endo- 
carditis was  produced  by  uric  acid  circulating  in  the  blood 

1  1 


2  INTRODUCTION 

or  by  a  disturbance  of  some  nervous  process  in  the  brain, 
or  as  a  result  of  a  surfeit  of  meat  or  carbohydrate  foods  ? 
The  rheumatic  nodule  so  well  recognised  as  a  very  character- 
istic lesion  in  childhood  lost  its  mystery  when  it  was  dis- 
covered that  it  can  be  experimentally  produced  by  intravenous 
inoculation  of  a  micrococcus  and  was  in  itself  a  complete 
rheumatic  lesion  upon  a  small  scale.  Chorea,  one  of  the  most 
remarkable  of  all  the  clinical  phenomena,  becomes  at  least 
more  comprehensible  when  we  find  that  in  the  same  patient 
a  micrococcus  isolated  from  an  acute  rheumatic  pericarditis 
may  also  be  discovered  in  the  pia  mater  and  brain,  and  further 
that,  when  inoculated  intravenously  into  animals,  it  may 
also  be  found  in  these  situations  producing  irregular  involuntary 
movements  by  virtue  of  the  tissue  changes  that  result.  It  is 
a  step  forward  and  surely  one  of  far  reaching  practical  im- 
portance that  we  can  now  state  with  confidence  that  a  micro- 
coccus gaining  access  to  the  system  from  an  inflamed  tonsil 
may  produce  heart  disease  with  or  without  the  involvement 
of  other  systems.  Every  medical  man  in  this  country  ac- 
quainted with  the  ravages  of  rheumatic  heart  disease  will,  we 
think,  recognise  that  in  the  establishment  of  such  a  fact  as 
this  and  with  the  proof  of  the  infective  origin  of  rheumatic 
carditis  there  is  brought  into  existence  a  new  hope  for  the 
victims  of  heart  disease.  No  marvellous  cure  indeed  declares 
itself,  but  great  possibilities  arise  for  the  best  of  all  treatment, 
that  of  prevention.  Those  who  are  deeply  interested  in  such, 
important  results  as  these  may  like  to  study  some  of  the  details 
of.  the  investigations  that  led  to  these  conclusions. 

Students  of  arthritis  will  recognise  that,  in  the  production 
by  intravenous  inoculation  of  non-suppurative  lesions  of 
joints  varying  both  in  intensity  and  duration,  the  great  field 
of  that  which  for  want  of  a  better  term  we  may  call  rheuma- 
toid arthritis  is  opened  out.  It  is  a  curious  result,  seeing  that 
we  first  demonstrated  non-suppurative  arthritis  as  an  out- 
come of  experimentation  with  a  micrococcus  obtained  from 


INTRODUCTION       •  3 

obvious  rheumatic  lesions,  that  often  enough  at  the  present 
time  the  term  "infective  arthritis"  is  used  to  express  a 
condition  which  is  to  be  differentiated  from  acute  rheumatic 
arthritis.  Time  alone  will  rectify  this  perversion  of  our 
interpretation  and  we  feel  that  we  must  be  content  with  the 
belief  that  these  fundamental  experiments  have  cleared  away 
some  of  the  mysteries  surrounding  "  rheumatoid  arthritis." 
Three  observations  in  the  problem  of  arthritis  are  of  particular 
importance,  one  is  that  the  same  infective  agent  may  produce 
all  varieties  of  non-suppurative  arthritis  from  a  simple  synovitis 
to  an  osteo-arthritis  ;  another  that  the  acute  and  very  chronic 
lesions  produced  by  experiment  may  be  associated  with 
effusions  which  are  sterile,  and  the  third  that  an  intravenous 
infection  may  produce  a  monarticular  arthritis. 

Another  aspect  of  the  subject  of  acute  rheumatism  worthy 
of  attention  and  brought  into  prominence  by  these  papers  is 
the  variety  of  lesions  produced  by  the  infection.  Undoubtedly 
it  resembles  its  allies  in  possessing  a  proclivity  for  attacking 
certain  of  the  tissues,  but  from  the  nature  of  its  pathology 
there  is  no  theoretical  barrier  to  the  possibility  of  its  attacking 
any  tissue  or  system  in  the  body.  We  are  accordingly  justi- 
fied in  studying  the  disease  upon  the  broadest  lines,  and 
with  minds  alert  to  the  possibility  that  there  are  in  man  rheu- 
matic affections  which  are  as  yet  hardly  accepted  as  of  that 
nature,  for  example  a  broncho-pneumonia,  a  nephritis,  a 
peritonitis  or  an  appendicitis.  Again  it  is  important  to 
remember  that,  if  this  infection  is  of  the  nature  we  believe 
it  to  be,  it  will  probably  show  in  the  tissues  all  grades  of 
virulence.  To  us  it  has  long  seemed  clear  that  the  nature 
of  the  rheumatic  processes  has  been  judged  too  rigidly  by  the 
criterion  of  the  acute  arthritis.  This  particular  phase  of  the 
infection,  frequent  enough  we  admit,  has  been  looked  upon 
as  representing  the  life  history  of  the  disease  and  this  view 
has  been  encouraged  by  the  relief  given  to  this  particular 
phase  by  the  salicylate  treatment.     With  this  view  however, 


4  INTRODUCTION 

we  are  not  in  accord  and  believe  that  on  insufficient  grounds 
cases  of  stubborn  non-suppurative  arthritis  have  been  declared 
to  be  non-rheumatic  in  nature. 

This  question  becomes  one  of  far  greater  importance  when 
endocardial  lesions  are  considered,  and  to  us  it  has  seemed  to 
be  unlikely  that  a  rheumatic  endocarditis  need  be  necessarily 
a  benign  or  healing  lesion.  To  this  important  point  we  have 
devoted  some  of  the  most  elaborate  of  our  papers. 

The  problems  in  the  bacteriology  of  rheumatism  are  both 
difficult  and  fascinating  and  it  is  only  due  to  ourselves  to  point 
out  that  new  facts  have  necessarily  been  forthcoming  in  this 
comparatively  young  science  during  the  fifteen  years  covered 
by    these   investigations.     Accordingly    the    bacteriologist    of 
to-day  will  not  expect  to  find  in  a  paper  written  in  1900  the 
details  that  are  demanded  now.     It  may  be  said  that  bacteri- 
ology in  this  country  was  only  in  its  very  infancy  at  the  time 
that  we  were  students  and  that  then  necessarily  much  im- 
portance was  attached  to  certain  standards  which  the  natural 
development  of    the  science  have  shown  to  be  too  arbitrary 
Certain  staining  methods  and  certain  morphological  details 
for  example  became  looked  upon  as  tests  of  the  specificity  of 
various  micro-organisms  and  sometimes  on  insufficient  grounds 
the    specific    micro-organism    and    the    specific    disease    were 
looked  upon  as  almost  identical  in  the  sense  that  the  disease 
was   thought    to   be   entirely   dependent    upon   the   infective 
agent.     The  pos:-ibility  of  the  evolution  of  micro-organisms 
was  in  danger  of  being  overlooked.     There  can  be  no  doubt 
that   circumstances  may   arise  in   which   the   virulence  of   a 
micro-organism  may  become  so  extreme  and  so  special  that  it 
may   overcome   the   most   healthy   and   destroy   them   by   a 
disease  which  runs  a  peculiar  course,  but  it  is  also  clear  that 
in  many  instances  a  micro-organism,  though  to  tests  in  vitro 
and  in  its  morphology  apparently  unaltered,  may  lose  entirely 
its  specific  powers  and  revert  to  a  saprophytic  state.     Again  it 
is  recognised  that  the  specific  virulence  may  greatly  depend 


INTRODUCTION  5 

upon  the  condition  of  the  host  at  the  time  of  infection.  Thus 
a  specific  infective  disease  may  be  by  no  means  entirely 
dependent  upon  the  particular  infective  agent,  for  it  may 
also  need  some  special  conditions  in  the  patient.  Because 
a  micro-organism  may  have  the  same  morphology  and  share  in 
common  certain  properties  in  vitro  with  one  believed  to  be 
specific  it  does  not  necessarily  follow  that  it  is  identical  in 
its  essential  property,  namely  the  ability  to  produce  a  par- 
ticular disease. 

These  difficulties  are  perhaps  at  their  greatest  in  the  strepto- 
coccal group,  but  when  our  first  papers  were  brought  forward 
this  group  was  but  partially  recognised  and  to  many  the  term 
"streptococcus"  suggested  the  streptococcus  pyogenes.  The 
complexity  of  this  group  is  now  thoroughly  appreciated,  but 
thirteen  years  ago  any  investigation  in  which  a  streptococcus 
was  claimed  as  the  cause  of  a  disease  was  in  the  greatest  danger 
of  being  brushed  aside  with  the  comment  that  the  authors 
had  rediscovered  the  streptococcus  pyogenes.  Recognising 
the  possible  fallacies  contained  in  the  term  "  specific  "  micro- 
organism, we  declined  to  go  further  than  to  claim  that  the 
diplococcus  we  had  isolated  was  the  only  cause  we  could 
find  of  a  specific  disease.  We  relied  and  still  rely  on  the 
belief  that  the  nearest  approach  that  can  be  reached  in  the 
establishment  of  the  causal  agency  of  any  micro-organism 
to  a  disease  is  the  isolation  of  it  from  the  acute  lesions  in 
man  and  the  reproduction  of  these  with  it  in  animals.  It 
is  not  a  perfect  test  and  from  the  standpoint  of  clinical  medicine 
in  some  respects  unsatisfactory.  But  the  results  obtained  in 
living  animals  under  these  circumstances  bring  us  we  believe 
nearer  the  truth  than  do  any  tests  of  a  micrococcus  outside 
the  living  body  conducted  in  the  laboratory. 

Such  an  attitude  as  this,  however,  demands  of  us  that  we 
bring  good  evidence  that  the  disease  we  claim  to  be  specific 
is  indeed  a  peculiar  one.  Our  investigations,  both  clinical 
and  pathological,  on  this  have  been  extensive  and  searching 


6  INTRODUCTION 

and  they  are  fortunate  in  receiving,  we  believe,  almost  the 
unanimous  support  in  this  country  of  those  who  are  thoroughly 
acquainted  with  rheumatism  studied  from  its  purest  source, 
its  occurrence  in  childhood.  Among  the  many  criticisms 
that  have  been  made  upon  the  investigations,  the  definite 
objection  that  acute  rheumatism  is  not  a  peculiar  disease  we 
have  been  prepared  to  meet  with  determination  and  con- 
viction by  the  statement  that  it  is  one  of  the  most 
special  and  definite  diseases  in  this  country,  although  it  is 
quite  possible  that  there  may  be  different  types  which  the 
future  will  determine  just  as  there  are  different  types  of 
pneumococcic  infection.  In  these  papers  we  have  devoted 
much  attention  to  these  problems  which  are  clearly  of  cardinal 
importance. 

There  is  another  important  result  of  our  attitude  towards 
this  question  and  one  to  which  we  are  anxious  to  draw  the 
reader's  particular  attention  for  it  limits  very  definitely  the 
scope  of  our  research.  We  have  never  claimed  that  the 
diplococcus  was  so  specific  in  its  cultural  and  laboratory 
tests  that  obtaining  a  micrococcus  morphologically  similar 
from  a  lesion  of  unknown  origin,  we  could  say  that  the  lesion 
was  rheumatic.  We  have  only  claimed  that  when  a  diplo- 
coccus with  such  characters  as  we  have  described  is  obtained 
from  a  lesion  of  undoubtedly  rheumatic  origin  and  produces 
the  experimental  lesions  of  this  disease,  that  it  is  the  causal 
agent.  With  the  utmost  caution  and  with  an  experience 
of  the  micrococcus  founded  upon  some  years  of  study  we 
have  isolated  it  from  the  diseased  tonsils  of  the  rheumatic, 
and  believe  that  we  have  proved  that  this  micrococcus  was 
identical  with  that  isolated  from  acute  rheumatic  lesions. 
But  we  are  well  aware  of  the  extreme  difficulty  of  this  step 
and  the  results  we  arrived  at  were  considered  with  this  diffi- 
culty fully  before  us.  We  would  point  out  that  we  have  never 
relied  upon  the  production  of  arthritis  in  rabbits  as  a  proof  of 
rheumatism,  as  any  who  read  our  first  paper  upon  the  aetiology 


INTRODUCTION  7 

will  at  once  recognise.  There  is  no  doubt  that  this  limitation 
in  the  research  is  a"  very  important  one  and  impairs  the  practical 
application  of  its  results,  but  we  have  not  been  primarily  con- 
cerned with  finding  a  "cure"  for  acute  rheumatism,  but 
rather  with  the  elucidation  of  the  nature  of  the  disease  and 
the  bearing  that  this  may  have  on  the  prevention  of  much 
heart  disease,  chorea  and  arthritis.  The  difficulties  presented 
by  the  streptococcal  group  of  micrococci  are  extreme,  and  such 
points  as  we  established  regarding  the  rapid  loss  of  virulence 
but  remarkable  resistance  in  the  saprophytic  stage,  the  size, 
the  staining  reactions  and  acid  producing  properties  of  the 
diplococcus  are  recorded  in  these  papers  and  have  met  with 
confirmation  from  others. 

We  have  answered  to  the  best  of  our  ability  the  numerous 
criticisms  that  we  have  encountered.  One  criticism  howrever 
it  is  impossible  to  answer  and  that  is  the  negative  results  that 
have  been  obtained  bv  manv  bacteriologists.  Such  a  question 
of  fact  can  onlv  be  met  bv  pointing  to  the  corroboration  of  our 
results  by  others. 

We  have  altered  but  little  in  the  original  papers  and  such 
alterations  as  have  been  made  are  chiefly  concerned  with  the 
prevention  of  wearisome  reiteration.  The  experimental  studies 
are  given  in  detail,  but  they  are  in  such  a  form  that  those  who 
wish  to  omit  them  can  easily  do  so.  A  few  alterations  have 
been  made  in  the  chronological  order  but  these  are  of  slight 
importance.  We  have  linked  the  papers  together  by  prefaces 
which  indicate  the  line  of  thought  and  the  new  facts  that  each 
contains.  The  various  contributions  are  grouped  into  three 
parts.  The  first  contains  those  papers  which  were  written 
before  the  demonstration  of  the  aetiology  and  which  were  steps 
antecedent  to  this.  The  second,  a  large  group,  contains  those 
which  demonstrate  the  aetiology  and  enquire  into  the  nature 
of  the  rheumatic  lesions,  both  human  and  experimental.  This 
group  is  subdivided  into  a  group  dealing  with  the  cardina 
steps  in  the  demonstration  of  the  aetiology  and  others  dealing 


S  INTRODUCTION 

with  arthritis,  chorea  and  other  nervous  manifestations,  and 
with  heart  disease.  Among  these  papers  also  are  some  which 
touch  upon  such  debated  problems  as  the  cause  of  osteo- 
arthritis, the  nature  of  multiple  infections,  and  appendicitis. 
The  last  group  contains  the  practical  applications  of  the 
investigation  to  clinical  medicine  and  public  health.  We 
have  included  the  first  group  because  two  of  the  papers  are  of 
some  historical  interest.  The  joint  one  with  Dr.  D.  B.  Lees 
on  acute  dilatation  of  the  heart  helped  to  place  on  a  firm  basis 
the  outstanding  importance  of  the  myocardium  in  rheumatic 
heart  disease.  The  pathological  investigation  on  the  myo- 
cardium demonstrated  the  occurrence  of  those  focal  lesions 
which  have  later  attracted  so  much  attention  under  the  name 
of  "  submiliary  nodules  "  in  connection  with  the  specific  cell 
of  the  rheumatic  lesions  and  the  mechanism  of  cardiac 
arrhythmias.  These  papers  also  favoured  the  view  that  the 
rheumatic  processes  were  the  results  of  an  infection.  Lastly 
reference  to  them  will  show  that  our  teachers  and  we  ourselves 
recognised  the  important  part  taken  by  the  myocardium  in 
heart  disease,  which  the  introduction  of  new  methods  has  of  late 
so  strongly  emphasised. 

The  difficulties  in  the  investigation  of  rheumatism  as  we 
have  met  with  them  are  considerable,  and  it  may  be  of  some 
service  to  others  if  we  mention  some  of  those  which  have 
chiefly  impressed  us.  Although  the  acute  disease  in  child- 
hood is  rife  in  this  country,  fatal  cases  are  not  very  frequent 
and  this  necessarily  makes  progress  slow.  Then  as  we  dis- 
covered by  experience  the  micrococcus  is  rapidly  destroyed 
by  the  living  tissues  and  the  favoured  sites  are  not  as  in 
tuberculosis  those  which  are  in  communication  with  the 
exterior  but  are  closed  cavities  such  as  the  pericardial,  synovial, 
and  cranial.  The  infection  is  moulded  on  the  pyaemic  type, 
that  is  it  produces  essentially  local  lesions,  and  this  combined 
with  the  great  resistance  of  the  tissues  makes  it  difficult  to  iso- 
late the  micrococcus  from  the  exudations  even  if  their  presence 


INTRODUCTION  9 

be  obvious  in  films.  Then,  again,  it  is  a  delicate  micrococcus, 
and  living  in  the  local  lesions  its  isolation  from  the  blood 
is  not  to  be  as  a  rule  expected,  and  the  maintenance  of  the 
virulence  we  have  found  difficult  and  have  repeatedly  directed 
attention  to  the  failure  of  peptone-agar  and  peptone-bouillon  as 
satisfactory  media.  The  demonstration  of  the  micro-organism 
in  the  tissues  is  not  easy  for  the  reason  given  above  and  because 
it  is  minute  and  not  tenacious  of  Gram's  stain.  Over  this 
point  we  had  many  difficulties  until  experimental  investi- 
gation came  to  our  assistance.  In  our  papers  we  have  re- 
peatedly dwelt  upon  these  difficulties  which  we  have  only 
succeeded  in  overcoming  by  the  closest  attention  to  all  details. 

There  was  another  initial  difficulty  not  perhaps  at  first  so 
apparent,  the  necessity  for  obtaining  some  firm  basis  from 
which  to  start.  It  is  clear  that  the  first  step  must  be  to 
obtain  some  position  or  some  guide  which  can  be  made  reason- 
ably safe  and  to  which  we  can  fall  back  for  support  and 
assistance.  The  acute  rheumatism  of  childhood  was  the 
basis  for  this  investigation,  because  it  is  frequent  in  its  occur- 
rence and  also  not  uncommonly  fatal,  and  thus  clinical,  patho- 
logical and  histological  facts  can  be  obtained.  The  greater 
part  of  this  book  is  concerned  with  the  details  of  this  disease, 
and  because  it  is  our  basis  we  have  opposed  with  the  utmost 
determination  any  attempts  to  make  us  draw  back  from  our 
contention  that  it  is  a  specific  disease.  If  this  point  is  yielded 
we  drop  back  once  more  into  the  chaos  of  those  disorders 
covered  by  the  all-embracing  term  "  rheumatism  "  and  much 
time  will  be  lost  then  in  disputing  as  to  what  is  to  be  looked 
upon  as  rheumatic. 

Those  who  have  not  paid  especial  attention  to  rheumatic 
affections  may  think  that  we  have  fallen  into  the  trap  of 
believing  that  everything  we  met  with  showing  the  least 
resemblance  to  acute  rheumatism  was  in  reality  of  that  nature. 
Such  however  is  not  the  case  :  we  certainly  have  ventured 
from  time  to  time  from  our  basis  to  explore  allied  disorder 


io  INTRODUCTION 

by  the  light  of  ascertained  facts  but  we  have  always  remem- 
bered that  these  ventures  were  tentative.  The  establishment 
of  the  cause  of  a  most  important  disease  among  those  classed 
in  general  terms  as  "  rheumatic  "  is,  we  believe,  the  first  and 
essential  step  in  the  study  of  the  problem  and  then  by  com- 
paratively easy  stages  the  remainder  of  the  group  will  be 
eventually  elucidated.  It  is  not  difficult  to  see  how  the 
horizon  widens  as  an  outcome  even  of  the  results  recorded 
here.  If  there  is  a  definite  infective  agent  for  some  form 
of  "rheumatism"  that  agent  must  differ  in  virulence  and 
resistance  in  different  cases,  and  in  these  possibilities  lies  a 
large  field  for  observation.  The  morbid  anatomy  resulting 
from  the  toxines  of  this  infection  will  serve  as  a  basis  for 
comparison  in  the  study  of  the  allied  disorders.  Again,  the 
results  of  multiple  infections  can  be  more  easily  interpreted 
when  the  results  of  the  simple  infection  are  understood. 

This  investigation  we  realise  only  touches  upon  the  greater 
problem  of  "  rheumatism."  We  have  not  thrown  light  upon 
the  actual  nature  of  the  toxines,  and  many  of  the  questions 
as  to  the  more  chronic  forms  of  arthritis  have  yet  to  be  ex- 
plained. The  field  is  a  very  wide  one  and  of  the  greatest 
interest  and  importance  in  this  country  in  which  rheumatism 
is  so  frequent. 


PART  I 

PAPERS  PUBLISHED  BETWEEN  1898  AND  1900,  PRE- 
VIOUS  TO   THE   DEMONSTRATION   OF   THE   DIPLO- 
COCCUS,  WHICH  WE  LOOK  UPON  AS  THE  BACTERIAL 
CAUSE  OF  ACUTE  RHEUMATISM 

I.  ACUTE  DILATATION  OF  THE  HEART  IN  THE  RHEUMA- 
TISM AND  CHOREA  OF  CHILDHOOD.     By  Dr.  D.  B.  Lees 
and  Dr.  F.  J.  Poynton 

II.  A  CASE  OF  RHEUMATIC  PERICARDITIS  AND  EXTREME 
DILATATION  OF  THE  HEART,  WITH  AN  INVESTI- 
GATION INTO  THE  MICROSCOPY  OF  RHEUMATIC 
HEART  DISEASE 

III.  A  STUDY     OF     THE   HEART-WALL     IN     DIPHTHERIA, 

RHEUMATIC  FEVER,  AND  CHOREA 

IV.  OBSERVATIONS  UPON  THE  PATHOLOGY  OF  THE  MYO- 

CARDIUM 

V.  THE  HISTOLOGY  OF  THE  RHEUMATIC  NODULE.  By 
Dr.  F.  J.  Poynton  and  Dr.  G.  F.  Still 

VI.  THREE  FATAL  CASES  OF  EXTENSIVE  VENOUS  THROM- 
BOSIS ASSOCIATED  WITH  SEVERE  RHEUMATIC  CAR- 
DITIS 

VII.  A    CASE    OF    VIRULENT    RHEUMATISM  WITH    EXTEN- 
SIVE PURPURA 


1 1 


PAPER  NO.   I 

ACUTE  DILATATION  OF  THE  HEART  IN  THE 

RHEUMATISM  AND   CHOREA  OF 

CHILDHOOD. 

By  D.  B.  LEES,  M.D.  and  F.  J.  POYNTON,  M.D. 

(From  vol.  lxxxi  of  the  Medico-Chirurgical  Transactions.) 

This  paper  upon  dilatation  of  the  heart,  inspired  and  collaborated 
in  by  Dr.  D.  B.  Lees,  gave  us  one  of  the  chief  clues  as  to  the  line  of 
subsequent  investigation.  For  the  demonstration  of  the  clinical 
importance  of  this  dilatation  in  rheumatism  suggested  a  resemblance 
between  the  behaviour  of  the  heart  in  this  disease  and  in  others  of 
undoubtedly  infective  origin.  Further,  the  view  was  favoured  that  a 
minute  study  of  the  myocardium  in  rheumatism  would  discover  lesions, 
which  in  their  turn  would  support  the  theory  that  the  process  was  of  an 
infective  nature. 

The  paper  itself  was  a  sequel  to  one  by  Dr.  D.  B.  Lees  upon  acute 
dilatation  of  the  heart  in  rheumatic  fever  read  the  same  evening.  The 
methods  of  investigation  that  were  employed  in  both  of  them  were 
identical,  and  their  intention  was  to  establish  on  a  clinical  basis  the 
reality  of  acute  dilatation  in  the  carditis  of  rheumatism,  and  also  to 
direct  attention  to  the  comparatively  minor  importance  of  pericardial 
effusion  as  an  explanation  of  the  great  increase  in  the  area  of  precordial 
dullness  that  may  occur  in  severe  carditis. 

The  extensive  analysis  of  fatal  cardiac  rheumatism  in  Appendix  C  , 
is  a  useful  reference  Table  for  the  study  of  the  various  lesions  that  may 
occur. 

This  paper  embodies  the  results  of  a  joint  investigation  of 
the  subject  of  acute  dilatation  of  the  heart  in  rheumatism 
and  chorea  made  at  the  Hospital  for  Sick  Children,  and  it 
also  includes  an  account  of  certain  enquiries  in  further  elucida- 
tion of  the  subject.     These  enquiries  comprise : 

i.  Observation  on  the  size,  strength,  and  sounds  of  the 
heart  in  healthy  children. 

13 


i4  ACUTE  DILATATION  OF  THE  HEART 

2.  Observations  on  the  condition  of  the  heart  in  rheumatic 
and  choreic  children  under  the  care  of  physicians  other  than  Dr. 
Lees.  We  tender  our  thanks  to  Dr.  Cheadle,  Dr.  Barlow, 
Dr.  Phillips,  and  Dr.  Penrose,  for  kind  permission  to  make 
use  of  their  case-. 

3.  An  analysis  of  150  fatal  cases  of  rheumatic  heart  disease 
in  children  under  twelve  years  of  age,  taken  from  the  records 
of  the  Hospital  for  Sick  Children  and  from  those  of  St.  Mary's 
Hospital. 

Before  proceeding  to  discuss  the  condition  of  the  heart  in 
rheumatic  and  choreic  children  we  wish,  in  order  to  obtain 
a  standard  of  comparison,  to  draw  attention  to  observations 
on  the  size,  strength,  and  sounds  of  the  heart  in  children  free 
from  rheumatism.  These  were  carried  out  partly  in  the 
surgical  wards  of  the  Hospital  for  Sick  Children,  in  forty-five 
cases  under  the  care  of  Mr.  Owen.  Mr.  Morgan,  and  Mr.  Pitts, 
who  kindly  allowed  us  to  use  their  patients  ;  and  partly  at 
Marlborough  College,  where  the  hearts  of  thirty-five  healthy 
boys  of  twelve  and  thirteen  years  were  examined  by  the 
permission  and  with  the  kind  assistance  of  Dr.  Penny, 
medical  officer  to  the  College,  to  whom  also  we  offer  our 
thanks. 

All  these  observations  were  made  with  the  child  in  the  same 
posture — on  the  back,  with  the  left  arm  abducted.  The 
results  are  given  in  detail  in  Appendices  A  and  B.  We  may 
briefly  summarise  them  as  follows  : 

In  children  aged  from  seven  to  twelve  years  the  area  of 
cardiac  dullness  (by  which  we  mean  the  nearest  approach  to  the 
actual  size  of  the  heart  that  can  be  obtained  by  percussion) 
extends  upward  to  the  third  costal  cartilage  on  the  left  side, 
thence  downward  and  to  the  left  to  the  fourth  space  just 
internal  to  the  nipple,  or  even  as  far  as  the  nipple-line.  Crossing 
the  middle  line  above,  it  extends  in  the  fourth  right  space  three 
quarters  of  an  inch  to  the  right  of  the  median  line,  a  bare 
iingerbreadth  to  the  right  of  the  sternal  margin.  As  it  passes 
downward  it  tends  slightly  inward  before  it  reaches  the 
hepatic  dullness,  and  then  recrosses  the  middle  line  to  reach 
the  apex. 

In  children  under  seven  years  of  age  the  cardiac  dullness 
extends  as  far  as  the  left  nipple-line  more  frequently  than  is 
the  case  in  older  children. 


IN  CHILDHOOD  15 

In  the  boys  between  twelve  and  fourteen,  the  left  limit 
of  the  cardiac  dullness  was  almost  invariably  distinctly  internal 
to  the  left  nipple-line,  on  the  average  about  three  quarters 
of  an  inch  from  it,  and  reached  the  fifth  left  rib  or  more  fre- 
quently the  fifth  space. 

In  healthy  children  the  cardiac  impulse  is  usually  internal 
to  the  left  limit  of  the  dullness,  often  markedly  so.  The 
action  of  the  heart  is  regular.  At  the  apex,  the  first  sound  is 
longer  than  the  second.  At  the  base,  the  second  sound  is 
louder  on  the  left  side  than  on  the  right,  though  both  have  a 
distinct  relative  sharpness.  Soft  blowing  systolic  murmurs 
are  sometimes  heard,  most  frequently  in  the  fourth  space 
internal  to  the  impulse,  sometimes  at  the  base,  more  rarely 
at  the  apex  ;  they  may  be  modified  by  position.  When  these 
murmurs  occur,  the  area  of  the  heart  is  often  rather  larger  than 
normal  the  general  physique  more  feeble,  and  the  child  anaemic. 

So  far  as  regards  the  position  of  the  cardiac  impulse  and  its 
relation  to  the  nipple,  in  younger  and  in  older  children,  our 
results  are  in  accord  with  those  of  Starck  and  of  Dr.  Archibald 
Garrod  quoted  by  the  late  Dr.  Sturgess  in  the  Lumleian  lectures 
in  1894.  But  in  determining  the  "  cardiac  dullness  "  we  have 
rejected  the  "  superficial  dullness  "  and  endeavoured  to  ascer- 
tain the  true  outline  of  the  heart. 

We  conclude  this  section  of  our  paper  by  showing  with 
the  lantern  the  area  of  cardiac  dullness  in  a  healthy  boy  of 

Healthy  boy,  aged  12. 
X*)H/pp/e 


twelve,  to  serve  as  a  standard  of  comparison  for  the  tracings 
taken  from  rheumatic  and  choreic  children. 

We  now  proceed  to  show  tracings  taken  from  the  hearts 
of  children  suffering  from  rheumatism  or  from  chorea,  and 
would  premise  that  the  several  tracings  in  each  case  were  always 
taken  without  reference  to  previous  tracings  from  the  same  case. 

The  varying  severity  of  the  cardiac  affection  makes  it 
desirable  to  arrange  our  observations  in  four  groups. 


i6 


ACUTE  DILATATION  OF  THE  HEART 


Group  I.  First  attacks  of  mild  subacute  rheumatism,  in  which 
there  was  no  pericarditis,  and  either  no  murmur  or  only  a 
systolic  murmur  best  heard  internal  to  the  nipple. 

(ask  i.  E.  S — -,  aged  12,  admitted  into  St.  Mary's  Hospital 
under  Dr.  Cheadle  October  9,  1897,  lor  moderate  articular 
rheumatism. 


E.  S — ,  aged  12.     Rheumatic  fever,  first  attack. 


A 

No.  2. 
Oct.  26,  1897. 


!   accentuated   pulmonary   second   sound. 

X      impulse. 


systolic   murmur. 


October  10.  First  tracing.  Temperature  normal.  Impulse 
in  the  V.N.L.  Area  as  shown.  Short  first  sound.  Accentuated 
pulmonary  second. 

16th.  A  slight  rise  of  temperature  (to  99.8°),  and  a  soft 
systolic  murmur  heard  internal  to  the  impulse. 

26th.  Second  tracing.  Steady  recovery  had  taken  place. 
Temperature  normal.  Impulse  internal  to  V.N.L.  Area  as 
shown.  Systolic  murmur  very  faint.  It  disappeared  two 
days  afterwards. 

Case  2.  F.  D — ,  aged  n,  admitted  into  St.  Mary's  under 
Dr.  Lees,  April  6,  1897,  with  mild  articular  rheumatism. 

F.  D — ,  aged  11.     Rheumatic  fever,  first  attack. 


A 

No.  1.  No.  2. 

April  7,  1897.  April  17.  1897. 

!  accentuated  pulmonary  second  sound.     *  systolic  murmur, 
x   impulse. 


IN  CHILDHOOD 


17 


April  yth.  First  tracing.  Temperature  102°.  Impulse 
diffuse,  Area  as  shown.  Soft  systolic  murmur  internal  to 
impulse.     Loud  pulmonary  second. 

8th.     Temperature  fell  to  normal. 

xyth.  The  boy  well.  Second  tracing.  Impulse  more 
definite,  and  internal  to  the  nipple.  Area  diminished.  No 
murmur. 


Case  3.  E.  D — ,  aged  9,  admitted  into  the  Hospital  for 
Sick  Children  under  Dr.  Lees,  February  29,  1896,  for  articular 
rheumatism. 

E.  D — ,  aged  9.     Rheumatic  fever,  first  attack. 


A 

No.  2.  No.  3. 

March  5,  1896.  April  7,  1896. 

!  accentuated  pulmonary  second  sound.     *  systolic  murmur, 
x    X   diffuse  impulse. 

March  1.  First  tracing.  Temperature  101.20.  Impulse 
diffused,  and  external  to  V.N.L.  Faint  systolic  murmur 
internal  to  the  impulse.     Loud  pulmonary  second. 

$th.  Second  tracing.  Increase  in  cardiac  area.  Salicylates 
were  now  pushed,  and  the  dilatation  slowly  subsided. 

April  7.  Third  tracing.  Impulse  definite  and  internal  to 
V.N.L.     Area  diminished.     Systolic  murmur  gone. 

Group  II.     First  attacks  of  chorea  without  history  of  previous 
rheumatism. 

The  occasional  occurrence  of  dilatation  of  the  heart  in 
chorea  has  been  noted  both  by  Dr.  Garrod  and  by  Dr.  Osier. 
We  find  that  it  is  common,  even  in  cases  in  which  there  is  no 
indication  of  rheumatism  other  than  the  chorea  and  no  history 
of  any  previous  rheumatic  attack.  In  thirty-three  cases 
without  history  of  previous  rheumatism,  and  in  many  of  them 
without  evidence  of  present  rheumatism,  we  found  that  the 
area  of  cardiac  dullness  extended  to  the  left  of  the  nipple-line 
(usually  about  one  finger-breadth)  in  no  fewer  than  twenty- 

2 


i8 


ACUTE  DILATATION  OF  THE  HEART 


nine,  and  in  sixteen  of  these  the  impulse  also  was  external  to 
the  nipple.  On  the  other  hand,  in  only  three  of  them  was 
there  evidence  of  increase  of  the  cardiac  dullness  towards  the 
right.  The  auscultatory  signs  were  noted  in  twenty-eight 
cases  ;  in  twenty-four  of  these  the  first  sound  was  short,  or 
accompanied  by  a  faint  systolic  murmur.  Tracings  were  taken 
in  all  the  thirty-three  cases,  but  a  day  was  always  allowed 
to  elapse  after  the  child's  admission  into  hospital  before  the 
first  determination  of  the  cardiac  outline  was  made.  We  now 
show  two  examples  illustrating  the  condition  of  the  heart  in 
typical  cases. 

Case  4.  \Y.  A — ,  aged  12,  admitted  into  St.  Mary's  Hospital, 
October  19,  1897,  under  Dr.  Lees,  for  chorea  of  moderate 
severity. 

W.  A.,  aged  12.     Chorea,  first  attack. 


A 

No.  1.  No.  2.  Xo.  3. 

Oct.  20,  1897.  Nov.  19,  1897.  Jan.  3,  1898. 

!  accentuated  pulmonary  second  sound.  *  systolic  murmur. 

x   impulse. 

October  20.  First  tracing.  Temperature  100. 2°.  Heart's 
action  irregular.  Impulse  external  to  nipple.  Area  as  shown. 
First  sound  remarkably  short.  Systolic  murmur  over  pul- 
monary artery  ;   loud  pulmonary  second. 

During  the  early  part  of  November  there  was  some  irregular 
pyrexia,  and  a  rheumatic  erythema  appeared. 

November  19.  Second  tracing.  The  area  had  increased, 
and  a  soft  blowing  murmur  could  be  heard  internal  to  the 
nipple.     After  this  there  was  gradual  and  slow  recovery. 

January  3, 1898.  Third  tracing.  Area  diminished.  Chorea 
and  murmur  gone. 


Case  5.     M.  M — ,  aged  10,  admitted  into  the  Hospital  for 


IN  CHILDHOOD  19 

Sick  Children,  March  17,  1896,   under   Dr.    Penrose.     Chorea 
distinct,  and  of  five  weeks  'duration. 


M.  M— , 

aged  10.      Chorea, 

first  attack. 

O 

O 

O 

No.  1. 

No.  2. 

No.  3. 

March  18,  1896. 

April  4,  1896. 

April  9,  1896. 

X    x   diffuse  impulse. 

x   impulse. 

.   systolic  murmur. 

March  18.  First  tracing.  Temperature  990.  Impulse  just 
internal  to  V.N.L.  Area  as  shown.  Basic  systolic  pulmonary 
murmur  ;    accentuated  second  sound. 

April  4.  Second  tracing.  Chorea  nearly  well.  Area  of 
dullness  much  diminished. 

gth.  Third  tracing.  The  child  had  been  getting  up,  but 
on  the  8th  had  a  little  pyrexia,  and  a  relapse  of  chorea.  She 
was  sent  back  to  bed.  This  tracing  shows  an  increase  in  the 
area. 

She  subsequently  entirely  recovered. 

It  is  clear,  therefore,  that  in  first  attacks  of  rheumatism 
and  in  first  attacks  of  chorea  there  is  often  a  definite  increase 
in  the  cardiac  area,  appearing  and  disappearing  under  observa- 
tion ;  there  is  also  an  outward  movement  of  the  impulse,  and 
an  accentuation  of  the  pulmonary  second  sound  ;  sometimes 
there  is  development  of  a  soft  systolic  murmur  internal  to  the 
nipple  ;  occasionally  there  is  irregularity.  Evidence  of  active 
rheumatism  may  be  present  also  ;  such  as  arthritis,  or  erythema 
or  there  may  be  pyrexia  alone.  It  is  in  such  a  combination 
of  signs,  more  or  less  developed,  that  such  hearts  differ  from 
the  normal  standard  ;  it  is  a  difference  which  is  distinct,  and 
the  earliest  appreciable  in  the  history  of  rheumatic  heart- 
disease.  It  cannot  be  explained  by  pyrexia,  for  it  may  be 
present  when  the  temperature  is  normal  ;  nor  by  the  effect 
of  salicylates,  for  it  is  present  before  treatment  has  been  com- 
menced ;  nor  in  cases  of  chorea  by  the  movements,  for  its 
amount  bears  no  constant  relation  to  the  severity  of  these. 
It  is  not  merely  a  part  of  the  debility  caused  by  an  illness,  for  it 


20 


ACUTE  DILATATION  OF  THE  HEART 


is  often  much  more  distinct  in  very  mild  attacks  of  rheumatism 
than  in  more  severe  diseases.  It  is  evidently  in  some  way  a 
special  result  of  the  rheumatic  process.  The  evidence  already 
given  appears  to  prove  that  it  is  independent  of  pericarditis. 
It  is  more  difficult  to  prove  the  absence  of  endocarditis,  but 
if  any  valvulitis  at  all  was  present  in  the  above  cases  it  must 
have  been  extremely  slight,  and  quite  incapable  of  producing 
so  definite  an  enlargement  of  the  heart,  or  one  capable  of  such 
easy  recovery.  It  seems  impossible  to  avoid  the  conclusion 
that  in  rheumatism  there  is  some  toxic  action  exerted  on  the 
cardiac  muscle,  enfeebling  it  and  causing  it  to  give  way  before 
the  normal  blood-pressure.  This  explains  why  the  first 
sound  becomes  short,  the  area  of  dullness  increased,  and  the 
impulse  diffused.  The  feebler  diastolic  rebound,  causing  a 
weaker  suction  action  in  diastole,  explains  why  the  pulmonary 
tension  rises,  and  the  pulmonary  second  becomes  accentuated. 
Before  passing  to  the  more  severe  rheumatic  cases,  which  we 
have  placed  in  the  third  group,  we  wish  to  give  an  example 
of  acute  dilatation  in  a  first  attack  of  chorea,  which  was  followed 
by  definite  valvulitis. 

Case  6.  L.  H — ,  aged  n,  admitted  into  hospital  August  19, 
1897,  under  Dr.  Lees,  for  moderate  chorea  of  two  weeks' 
standing. 

L.  H.,  aged  11.     Chorea,  first  attack. 


No.  1.  No.  2. 

Aug.  20,  1897.  Aug.  30,  1897. 

!  accentuated  pulmonary  second  sound.  *  systolic  murmur. 
— ►  systolic  murmur  conducted  to  axilla.  x  x  diffuse 
impulse. 

August  20.  First  tracing.  Temperature  990.  Impulse 
external  to  nipple.  Area  as  shown.  First  sound  short. 
Sounds  spaced.  A  very  faint  soft  murmur  heard  internal  to  the 
impulse. 

This  condition  continued  unchanged  for  ten  days.  On  the 
29th  the  temperature  rose  from  normal  to  99. 8°,  and  a  definite 
musical  blowing  murmur  appeared, 


IN  CHILDHOOD 


21 


30th.  Second  tracing.  Area  as  shown.  The  murmur  could 
be  traced  to  the  axilla,  and  all  who  examined  the  case  agreed 
that  there  was  now  definite  valvulitis.  When  the  patient  left 
the  hospital  a  month  later,  the  murmur  was  still  present  and 
audible  in  the  axilla. 

Group  III.     Severe  cases  of  acute  rheumatic  heart  disease,  with 
definite  valvulitis  and  frequently  pericarditis. 

We  give  tracings  from  two  cases  as  types  of  these  severe 
attacks. 

Case  7.  E.  C — ,  aged  11,  admitted  into  the  Hospital  for 
Sick  Children,  February  20,  1896,  under  Dr.  Penrose,  for  a 
severe  first  attack  of  chorea.  In  the  out-patient  department 
in  the  morning  no  murmur  was  heard,  but  later  in  the  day  a 
soft  apical  murmur  appeared. 

E.  C — ,  aged  1 1 .     Chorea  and  rheumatic  fever,  first  attack. 


No.  1. 
Feb.  21,  1896. 


& 


8 


No.  3. 
March  10,  189^ 
*  diastolic  murmur 


A 

No.  4. 
I.  April  22,  1896. 

8  to-and-fro  mitral  murmur, 
x   impulse. 


February  21.  First  tracing.  Temperature  10 1°.  Impulse 
external  to  nipple.  Area  as  shown.  A  to-and-fro  murmur 
audible  external  to  the  nipple.     Loud  pulmonary  second. 

23rd.     Erythema. 

2jth.     Arthritis. 

29th.  Second  tracing.  Temperature  990.  Area  slightly 
diminished.     For  some  days  the  aortic  second  had  been  short. 


22 


AC  I'll-:  DILATATION  OF  THE  HEART 


March  10.  Third  tracing.  Area  no  larger  than  before, 
though  a  well-marked  aortic  diastolic  murmur  had  developed. 
The  rheumatism  had  quieted  down. 

April  22.  Fourth  tracing.  After  decided  improvement 
there  were  now  fresh  pyrexia  and  joint  pains.  Area  decidedly 
increased.     Signs  of  aortic  disease  less  marked. 

Eventually  the  boy  recovered  sufficiently  to  leave  the 
hospital,  but  with  marked  aortic  and  mitral  regurgitation. 

In  this  case  there  was  no  evidence  of  pericarditis.  The 
increase  in  the  cardiac  dullness  was  most  marked  when  the 
rheumatism  was  most  active,  and  it  diminished  when  the 
rheumatism  subsided.  With  the  fresh  outburst  the  area 
again  became  enlarged.  If  the  dilatation  had  been  due 
to  the  valvular  lesions,  it  would  not  have  varied  in  this  way. 
but  would  have  steadily  and  gradually  increased  until  checked 
by  compensatory  hypertrophy. 


Case  8.     E.  B— ,  aged  8,  admitted  under  Dr.  Penrose  April 
ii,  1896,  for  general  pericarditis  and  chorea. 


E.  13 — ,  aged  8.     Chorea  and  rheumatic  fever,  first  attack. 


A 

No.  1.  Xo.  2.  No.  3. 

April  12,  1896.  April  iS,  1896.  April  J9,  1896. 

£  pericardial  friction.  x    x   diffuse  impulse. 

8  to-and-fro  mitral  murmur. 


April  12.  First  tracing.  Temperature  99  .  Xo  definite 
impulse  ;   area  as  shown  ;   loud  general  friction.     Very  ill. 

ijt/i.     Sharp  rales  over  front  of  left  lung. 

i8//z.  Second  tracing.  Area  diminished  ;  less  friction  ; 
a  double  murmur  at  the  apex. 

29^/7.  Third  tracing.  Remarkable  improvement  ;  chorea 
almost  gone".  Area  still  further  diminished.  No  friction  ; 
double  murmur  plainly  heard. 

June  8.  Discharged  ;  only  a  loud  systolic  murmur  remains  ; 
area  stiii  further  diminished. 


IN  CHILDHOOD  23 

In  this  case,  when  the  area  of  cardiac  dullness  was  most 
extensive,  the  pericardial  friction  was  loudest  and  most 
general.  This  suggests  that  there  was  probably  no  great 
excess  of  fluid  in  the  pericardial  cavity.  The  suggestion  is 
supported  by  the  post-mortem  records  of  fatal  cases  of  rheu- 
matic heart  disease.  In  only  12  out  of  150  cases  (see  Appendix 
C)  is  it  definitely  stated  that  more  than  two  ounces  of  fluid 
were  found  in  the  pericardial  cavity.  By  actual  experiment 
on  the  cadaver  we  have  ascertained  that  this  quantity  will 
not  produce  anything  like  the  enlargement  of  the  cardiac  area 
often  observed  during  life.  Dr.  Sibson  found  that  six  ounces 
of  fluid  were  required  to  distend  the  pericardium  in  a  boy  of 
nine.  If  to  these  facts  we  add  the  clinical  observation  that 
the  area  of  pulsation,  in  these  cases,  is  usually  extensive  and  the 
cardiac  sounds  fairly  loud,  we  are  driven  to  the  conclusion 
that  in  the  great  majority  of  cases  of  rheumatic  pericarditis 
the  increase  in  the  area  of  cardiac  dullness  is  mainly  due  to 
dilatation.  At  first  sight  it  might  seem  that  the  dilatation 
is  secondary  to  the  pericarditis,  but  it  is  much  less  marked 
in  suppurative  than  in  rheumatic  pericarditis,  and  it  is  often 
marked  in  rheumatism  in  which  no  pericarditis  exists.  We 
conclude,  therefore,  that^the  enfeeblement  of  the  cardiac  wall 
is  mainly  due  to  a  direct  toxic  action  of  the  rheumatic  poison. 
However  brought  about,  the  dilatation  is  a  most  serious  addition 
to  the  valvulitis  or  the  pericarditis  which  may  accompany  it, 
and  takes  a  very  large  share  in  the  production  of  the  dangerous 
symptoms  usually  attributed  to  them. 

Group  IV.     The  more  chronic  forms  of  chorea  and  rheumatism. 

Careful  observation  of  the  clinical  course  of  these  more  chronic 
cases,  and  comparison  with  the  results  revealed  by  post-mortem 
examination,  prove  that  in  them  also  dilatation  of  the  heart 
is  one  of  the  most  important  factors.  A  moderate  valve  lesion 
in  a  child  is  easily  and  effectually  compensated  if  no  fresh 
incidence  of  rheumatism  occurs.  On  the  other  hand,  grave 
symptoms  of  cardiac  failure  in  a  rheumatic  child  are  almost 
always  accompanied  by  fresh  rheumatic  manifestations.  In 
100  such  cases  ending  fatally  (Appendix  C)  there  was  evidence 
(apart  from  endocarditis)  of  fresh  rheumatism  in  86.  We  lay 
special  stress  on  this  fact,  for  it  indicates  that  in  children  the 


24 


ACUTE  DILATATION  OF  THE  HEART 


fatal  issue  of  rheumatic  heart  disease  is  not  often  the  mechanical 
result  of  damaged  valves,  as  is  frequently  the  case  in  adults, 
and  that  some  other  explanation  of  the  acute  cardiac  failure  is 
required.  And  this  is  confirmed  by  the  fact  that  the  amount 
of  change  in  the  valves  in  such  cases  is  usually  moderate  or 
slight.  The  chief  cause  of  the  fatal  issue  is  indicated  by  the 
analysis  of  150  autopsies  in  Appendix  C,  in  which  dilatation 
of  the  heart  is  specially  mentioned  in  92,  while  hypertrophy 
is  noted  in  only  58. 

The  progress  of  rheumatism,  as  seen  in  hospital,  fully  supports 
this  view.  The  cases  which  end  fatally  often  present,  during 
a  course  of  several  months,  a  series  of  rheumatic  exacerbations, 
— now  nodules,  now  arthritis,  now  pericarditis.  The  heart 
enlarges  immensely,  and  the  enlargement  occurs  synchronously 
with  the  rheumatic  exacerbations.  When  they  quiet  down  it 
ceases,  and  the  area  may  even  diminish.  This  enlargement  is 
not  a  hypertrophy  ;  the  physical  signs  and  the  prostration  of 
the  patient  prove  that  it  is  a  heart-failure,  and  therefore 
a  dilatation. 

On  the  other  hand,  when  no  fresh  rheumatic  manifestation 
occurs,  there  is  rarely  any  rapid  increase  of  the  cardiac  area, 
even  though  valvulitis  exists. 

In  chronic  cases,  then,  if  they  are  to  prove  fatal,  the  course 
is  one  of  frequent  rheumatic  manifestations  along  with  acute 
dilatations  of  the  heart  of  greater  or  less  severity. 

In  illustration  of  the  above  remarks  we  now  give  tracings 
from  two  chronic  cases. 

Case  9.  M.  P — ,  aged  9,  admitted  into  the  Hospital  for 
Sick  Children,  October  25,  1895,  under  Dr.  Penrose,  for  chorea. 
She  remained  in  the  hospital  until  November  30,  then  was  sent 
to  the  Highgate  Convalescent  Home,  much  better,  but  not 


M.  P— 

aged 

9.     Chronic  chorea. 

i 

O  ) 

) 

^     A 

r* 

k 

No.  1. 

No.  2.                              No.  3. 

'C 

b.  9,  1896. 

Mai 

ch  3,  1896.                Apri 

1 21.  [896. 

!  accentuated  pulmonary  second  sound.       x    x   impulse  diffuse. 


IN  CHILDHOOD  25 

well.  She  was  readmitted  February  6,  1896,  with  pain  in  the 
side,  and  increase  of  the  chorea,  which  had  never  disappeared. 

February  9.     First  tracing.     Chorea  severe.     Area  as  shown. 

March  3.  Second  tracing.  Chorea  still  severe.  A  soft 
murmur  now  heard  internal  to  nipple.  Area  further  increased. 
■  April  21.  Third  tracing.  Chorea  gone,  after  six  months' 
duration.     Area  considerably  diminished. 

Case  10.  W.  M — ,  aged  8,  admitted  into  the  Hospital  for 
Sick  Children,  December  4,  1895,  under  Dr.  Penrose  for  chorea, 
endocarditis,  and  doubtful  pericarditis  ;  the  attack  dated  from 
October. 

W.  M — ,  aged  8.     Subacute  rheumatic  fever,  second  attack. 


o 

.X' 

A 

Xo.  1.  Xo.  2.  Xo.  3. 

Dec.  5,  1S95.         March  26,  1896.  April  21,  1S96. 

!  accentuated  pulmonary  second  sound.      x  impulse. 
8  to-and-fro  mitral  murmur. 

December  5.  First  tracing.  Area  as  shown.  Organic  mitral 
murmur  and  doubtful  pericardial  friction. 

Throughout  December  and  January  the  chorea  persisted, 
with  slight  irregular  pyrexia  ;  once  in  January  what  appeared 
to  be  pericardial  friction  was  heard,  and  nodules  were  found. 
During  the  whole  of  February  the  child  lay  in  bed,  pale  and 
speechless,  with  slight  chorea  ;  more  nodules  developed,  and 
fresh  pyrexia.     Several  cardiac  tracings  were  taken. 

March  26,  1896.  Second  tracing.  Area  much  enlarged. 
Xodules  still  appearing. 

During  April  he  began  slowly  to  improve,  and  the  rheumatic 
symptoms  to  disappear. 

April  21.     Third  tracing.     Area  diminishing. 

The  improvement  continued,  and  he  recovered  sufficiently 
to  leave  the  hospital. 

Throughout  the  case  all  the  symptoms  pointed  to  dilatation 
of  the  heart,  and  not  to  hypertrophy  or  to  pericardial  effusion. 


26  ACUTE  DILATATION  OF  THE  HEART 

It  is  extremely  probable  that  the  pericardium  was  completely 
adherent,  for  in  150  fatal  cases,  acute  and  chronic,  it  was 
found  totally  adherent  in  seventy-seven  (see  Appendix  C). 
But  it  is  doubtful  how  far  even  a  completely  adherent  peri- 
cardium is  in  itself  a  cause  of  cardiac  dilatation.  In  the  records 
of  St.  Mary's  Hospital  we  find  thirty-four  cases  of  entire 
adhesion  of  the  pericardium  discovered  post  mortem  at  ages 
between  fifty  and  eighty-seven.  (In  none  of  these  patients 
were  the  kidneys  granular.)  Eighteen  of  these  patients  died 
from  causes  unconnected  with  the  heart. 

In  bringing  to  a  close  our  series  of  cardiac  tracings,  we 
would  again  draw  attention  to  the  evidence  of  the  frequency 
and  importance  of  dilatation  afforded  by  the  post-mor- 
tem records.  We  give  brief  notes  of  the  condition  found  in 
three  acutely  fatal  cases,  from  a  list  of  fifteen  such  given  in 
Appendix  C. 

1.  T.  G — ,  aged  7.  Recent  pericarditis,  the  pericardium 
partially  adherent  and  granular.  Marked  dilatation.  The 
mitral  valve  moderately  thickened  but  functional.  The 
aortic  valves  thickened.     The  myocardium  pale. 

2.  T.  B — ,  aged  10.  Pericarditis  with  much  recent  adhesion 
and  a  little  fluid.  Fine  granulations  on  the  aortic  valves 
and  on  the  mitral  flaps.  All  the  cavities  dilated.  The  muscle 
granular. 

3.  H.  U — ,  aged  9.  General  pericarditis,  recent  and  adhesive. 
Old  vegetations  on  the  mitral,  but  no  stenosis.  Aortic  valves 
thickened.     General  dilatation. 

In  each  of  these  dilatation  is  a  prominent  feature,  and  valvular 
changes  insignificant. 

From  the  clinical  records  of  these  cases  we  find  that  death 
is  often  rapid,  frequently  sudden  and  unexpected,  and  preceded 
by  pallor,  collapse,  vomiting,  delirium,  and  restlessness,  all 
pointing  to  grave  circulatory  failure.  Active  rheumatism 
is  almost  invariably  present.  Much  excess  of  pericardial  fluid 
is  rare.  Valvular  change  is  usually  moderate.  Dilatation 
is  more  marked  than  hypertrophy. 

The  recognition  of  rheumatic  dilatation  may  sometimes  be  of 
service  in  the  diagnosis  of  an  arthritis  of  otherwise  doubtful 
nature.  In  July  1896,  a  girl  aged  n  was  admitted  into  the 
Hospital  for  Sick  Children  under  Mr.  Morgan,  for  an  acute 
arthritis  of  the  right  hip-joint.     No  other  joint  was  affected. 


IN  CHILDHOOD  27 

The  thigh  was  swollen  and  excessively  painful.  Pyrexia  was 
present.  Acute  tubercular  disease  of  the  joint  was  suspected, 
but  the  area  of  cardiac  dullness  was  enlarged,  as  seen  in  the 
subjoined  tracing,  and  there  was  a  soft  systolic  murmur  external 
to  the  apex.  Extension  was  applied  and  salicylates  given. 
Next  day  two  interphalangeal  joints  of  the  toes  of  the  left  foot 
were  swollen.  The  affection  was  undoubtedly  rheumatic, 
and  the  child  was  rapidly  and  completely  cured  by  salicylates. 
We  are  indebted  to  Mr.  Morgan  for  permission  to  quote  this  case. 
From  the  point  of  view  of  prognosis,  the  recognition  of  acute 
dilatation  is  of  great  importance.     The  occurrence  of  a  second 

Girl  aged  1 1 .     Rheumatic  fever,  first  attack. 

7 


July  1896. 
!  accentuated  pulmonary  second  sound.       x   impulse. 
*  systolic  murmur. 

attack  of  rheumatism,  attended  by  an  acute  dilatation,  may 
entirely  upset  calculations  founded  merely  on  an  estimation 
of  the  valvular  damage  remaining  from  the  first  attack.  The 
possibility  of  a  fresh  rheumatic  attack,  causing  increased  dila- 
tation, is  by  far  the  most  important  element  in  the  prognosis. 

Finally,  with  regard  to  treatment,  we  would  point  out 
that  acute  dilatation  is  often  the  earliest  indication  of  a  rheu- 
matic heart  affection.  If,  as  we  believe,  salicylate  of  soda  is 
a  specific  for  rheumatism,  and  not  a  mere  allayer  of  pain,  it  is 
clearly  of  the  utmost  importance  to  give  this  drug  in  sufficient 
doses  as  soon  as  the  earliest  indication  of  the  pernicious  action 
of  rheumatism  on  the  heart  is  manifested. 

The  recognition  of  dilatation  will  also  make  us  lay  greater 
stress  on  the  necessity  for  rest  in  the  treatment  both  of  rheu- 
matism and  of  chorea.  And  when  the  question  of  the  advisa- 
bility of  paracentesis  pericardii  is  being  considered,  the  remem- 
brance of  the  frequency  of  marked  dilatation  and  of  the 
rarity  of  much  excess  of  fluid  in  the  pericardial  cavity  may 
save  us  from  a  therapeutic  disaster  which  has  befallen  more 
than  one  skilled  physician  in  the  past. 


28 


ACUTE  DILATATION  OF  THE  HEART 


APPENDIX  A 

Observations  upon  the  condition  of  the  heart  in  forty-five  children 
suffering  from  surgical  ailments  of  slight  severity,  and  free 
from  any  disease  of  the  chest.  These  observations  were 
made  at  the  Hospital  for  Sick  Children,  Great  Ormond  Street, 
May  to  November,  1896. 

The  exact  method  adopted  was  as  follows  :  A  tracing  of  the 
deep  cardiac  dullness  was  made  in  every  case.  The  child  was 
previously  kept  in  bed  for  a  day  at  least  after  admission  to  the 
hospital.  The  dullness  was  percussed  from  the  left  side,  the 
patient  lying  on  the  back  with  the  arm  abducted  and  chest 
quite  uncovered.  The  area  was  marked  out  as  delineated 
with  a  dermatographical  pencil  ;  the  impulse,  left  nipple,  and 
mid-sternum  were  indicated,  together  with  the  costal  angle. 
The  condition  of  the  sounds  and  any  peculiarity  of  the  chest 
or  physique  were  also  recorded.  Finally,  the  outline  was 
at  once  transferred  to  tracing  paper  and  dated. 

The  results  obtained  are  as  follows  : 

I.  The  ages  of  the  children  : 


Between  n  and  12  years 


10    ,, 

11     >, 

9    .- 

10     ,, 

8     „ 

9    -- 

7     » 

8     „ 

6     „ 

7     » 

5     „ 

6     „ 

4     ,. 

5     >> 

0 

0     " 

4     » 

2  and 

3  years 

1     ,, 

2     ,, 

10  cases 
6     „ 

5  u 

5  „ 

3  ., 

8  „ 

2  ,, 

1  case 

3  cases 
1  case 
1     ,, 


45 


II.  The  particular  surgical  ai 
Early  morbus  coxae 
Hydrocele 
Rectal  polypus 
Early  tubercular  knee 
Congenital  torticollis 


ments 


IN  CHILDHOOD 


29 


Early  spinal  caries 

1 

Radical  operations  for  hernia 

1 

Cleft  palate 

4 

Rickets 

3 

Functional  affection 

1 

Tubercular  glands    . 

4 

Adhesions  in  elbow-joint 

4 

Chronic  abscess      '  . 

4 

Old  excision  of  knee 

1 

Lupus  of  skin 

1 

Gummata  over  clavicle     . 

2 

Ranula 

1 
0 

Talipes  .... 
Nsevus   .... 

1 

Hammer-toe 

1 

Fracture 

1 

Total 


45 


III.  Distances  from  the  mid  sternum  to  the  nipple. 

Ages  :  11 — 12,  from  2\  to  3^  inches 

10 — 11, 

9 — io, 

8-  9> 

7-8, 

6-7, 
5-  6, 
1—  5, 


,,      2\ 

,  3 

„    2i 

,  3 

„       2i 

,  3 

„      2\ 

2^ 

„      2i 

2^ 

„      2i 

,    2\        ,, 

„      2i 

,    2\        „ 

IV.  A  line  drawn  at  a  right  angle  to  the  mid-sternal  line 
at  the  uppermost  limit  of  the  tracing  passed  through  the — 
Third  rib  on  the  left  side  in     .  .  .     37  cases. 

Second  space       ,,  7 

Third  space  ,,  ,,         .  .  .1    case. 


45 

V.  The  distance  from  the  mid-sternum  to  the  furthest  limit 
of  the  heart  to  the  right  : 

J  inch  in                .          .          .          .          .2  cases. 
\      >, 19      » 


30  ACUTE  DILATATION  OF  THE  HEART 

|  inch  in  .  .  .  .  13  cases 

I     „      „ 8     „ 

l£  inches  in  .....       1  case. 

Doubtful  in  .....       2  cases. 

45 
The  right  limit  of  the  heart  is  not  always  easily  ascertained, 
either  because  the  chest  is  misshapen  or  because  there  is 
considerable  emphysema.  These  difficulties  are,  however, 
exceptional  ;  if  the  chest  is  misshapen  it  may  be  difficult  to 
ascertain  any  limit  of  the  cardiac  dullness. 

The  right  limit  of  the  cardiac  dullness  in  children  is  normally 
about  one  fingerbreadth  to  the  right  of  the  right  margin  of  the 
sternum,  as  ascertained  by  percussion.  But  as  this  limit  is 
traced  from  above  downward  it  tends  inward  a  little  toward 
the  middle  line,  following  the  curve  of  the  auricle.  In  the 
healthy  heart  this  is  a  difficult  point  to  ascertain.  When  the 
heart  is  dilated  it  is  more  easily  appreciated,  but  even  then  may 
be  difficult  to  demonstrate  with  certainty. 

VI.  The  relation  of  the  left  limit  of  the  cardiac  dullness  to 
the  left  vertical  nipple-line  : 

Internal  to  the  nipple  in  19  cases. 

In  the  nipple  line  in  .  .  18      „ 

External  to  the  nipple  in         .  .  8      ,, 

45 
Six  of  the  8  cases  in  which  the  dullness  extended  outside 
the  nipple  line  were  under  six  years  of  age.     The  exact  measure- 
ments in  the  eight  cases  were  : 

}  inch  in  .  .  .  .4 

L  2 

8 

In  3  of  these  cases  the  children  appeared  normal,  in  3  the 
chest  was  noted  as  small  and  narrow,  in  2  the  children  were 
weak  and  delicate. 

It  should  be  stated  that  in  several  cases  a  small,  narrow  chest 
was  noted,  but  the  left  limit  was  internal  to  the  nipple-line. 


IN  CHILDHOOD  31 

VII.  The  relation  of  the  impulse  to  the  cardiac  dullness. 
This  is  often  considerably  internal  to  the  left  limit  of  the  cardiac 
dullness  ; 

Thus,  of  25  cases,  in  17  it  was  internal  to  this  left  limit,  in 
2  it  was  traced  outward  as  far  as  the  limit,  in  6  it  was  absent 
to  touch. 

VIII.  The  sounds. 

The  first  sound  was  usually  distinctly  longer  than  the 
second  sound.  The  second  sound  to  the  left  of  the  sternum 
at  the  base  was  usually  louder  than  the  second  sound  in  the 
second  right  space. 

In  twelve  cases  the  greater  loudness  of  the  pulmonary 
second  sound  was  especially  noted. 

IX.  Irregularity  of  the  heart  was  exceptional. 

X.  Bruits  were  found  in  some  cases. 

In  10  an  occasional  soft  systolic  murmur  was  heard  in  the 
fourth  space  just  to  the  left  of  the  sternum. 

In  6  a  systolic  murmur  was  heard  at  the  base  on  the  left  side. 


APPENDIX  B 

Observations   upon  the  hearts  of  35  healthy  public-schoolboys 
between    the    ages    of   twelve    and   fourteen. 

We  realised  that  cases  in  the  surgical  wards  of  an  hospital, 
though  free  from  chest  affections,  are  not  perfectly  healthy 
children.  We  have  accordingly  supplemented  the  results 
given  in  Appendix  A  with  the  following  observations  upon 
healthy  schoolboys  at  Marlborough  College.  We  are  much 
indebted  for  permission  to  Dr.  Penny,  Medical  Officer  to  the 
school. 

In  these  cases  tracings  were  not  taken,  but  the  distances 
were  noted  as  each  cardiac  area  was  percussed.  The  order 
of  examination,  as  in  previous  cases,  was  firstly,  palpation  ; 
secondly,  percussion  ;  thirdly  auscultation.  The  same  posture, 
namely,  the  supine  with  the  left  arm  abducted,  was  adopted 
as  in  the  previous  investigations  in  Appendix  A. 

The  results  obtained  were  as  follows  : 

I.  The  ages  :  between  twelve  and  thirteen  years,  4  ;  between 
thirteen  and  fourteen  years,  31. 


32  ACUTE  DILATATION  OF  THE  HEART 

II.  The  action  of  the  heart  was  regular,  except  in  the  case 
of  one  nervous  bov.  In  this  case  the  irregularity  soon  passed 
off. 

III.  The  position  of  the  impulse  in  relation  to  the  vertical 
nipple-line  and  to  the  ribs  : 

In  the  fifth  space  in  .  •  .23  cases 

At  the  fifth  rib  in      .  .  6      , 

In  the  fourth  space  in  .  .       4      ,, 

Not  localised  in  .  .  .       2      ,, 

The  impulse  was  internal  to  the  vertical  nipple-line  in  32 
cases,  and  frequently  considerably  so. 

Of  the  3  cases  in  which  the  impulse  was  felt  in  the  vertical 
nipple-line,  in  1  case  the  boy  was  delicate  and  in  the  doctor's 
house,  though  in  good  health  at  the  time. 

Case  2  and  Case  3  had  suffered  from  influenza  six  weeks 
before.  This  fact  was  of  especial  interest,  because  the  con- 
dition of  the  heart  had  been  ascertained  in  entire  ignorance 
of  this  history  of  influenza. 

IV.  The  deep  cardiac  dullness. 

(a)  The  left  limit  :  in  these  boys  with  well-formed  chests 
this  area  was  obtained  with  considerable  ease. 

(a)  In  21  cases  the  left  limit  was  about  one  inch  internal 
to  the  nipple. 

(b)  In  7  cases  it  reached  a  vertical  line  through  the  inner 
margin  of  the  areola. 

(c)  In  5  cases  it  reached  the  vertical  nipple-line. 

(d)  In  2  cases  it  reached  external  to  the  vertical  nipple-line, 
i.  Of  these  two  latter  cases,  in  one  limit  extended  \  inch 

external,  in  one  the  limit  extended  1  inch  external. 

One  of  these  boys  was  the  delicate  boy  already  mentioned, 
and  in  his  case  there  were  also  soft  systolic  murmurs  at  the 
base  and  apex. 

The  other  boy  had  suffered  from  an  attack  of  influenza  six 
weeks  previously  ;  he  had  also  a  soft  systolic  murmur  in  the 
fourth  space  internal  to  the  nipple. 

ii.  Of  the  5  cases  in  which  the  dullness  reached  the  vertical 
nipple-line,  in  each  there  was  a  soft  systolic  murmur  internal 
to  the  nipple. 

iii.  Of  the  7  cases  in  which  the  dullness  extended  almost  to 
the  vertical  nipple-line,  in  four  there  was  a  soft  systolic  murmur 


IN  CHILDHOOD  33 

internal  to  the  nipple,  and  in  one  the  first  sound  was  slightly 
blurred. 

iv.  Of  the  21  cases  in  which  the  dullness  at  its  left  limit  was 
distinctly  internal  to  the  vertical  nipple-line,  in  only  two  a  soft 
systolic  murmur  was  noted  internal  to  the  nipple. 

(b)  The  right  limit  :  in  4  cases  hyper-resonance  prevented 
the  limit  being  defined. 

In  2  cases  the  limit  was  ij  inches  from  the  mid-sternum. 
In  29  cases  the  limit  was  from  £  to  1  inch  to  the  right  of  the 
mid-sternum. 

(c)  The  upward  limit  to  the  left  of  the  sternum. 
The  third  rib  in  34  cases,  the  second  space  in  1  case. 

V.  The  sounds. 

In  5  cases  the  first  sound  at  the  apex  was  rather  short . 

The  second  sound  over  the  left  second  space  was  almost 
invariably  louder  than  over  the  right  second  space,  but  both 
were  well  defined  and  sharp. 

In  the  cases  with  soft  systolic  murmurs  the  second  sound 
to  the  left  was  especially  louder  than  that  to  the  right. 

VI.  Murmurs.  There  was  not  a  musical  murmur  in  any  of 
these  cases ;  they  were  all  soft  blowing  murmurs,  some 
diminished  by  the  erect  posture. 

The  situation  in  which  they  were  heard  most  frequently 
and  at  their  loudest  was  in  the  fourth  space  close  to  the  left 
margin  of  the  sternum.  This  murmur  became  fainter  when 
traced  to  the  nipple,  and  in  only  one  case  was  heard  external 
to  it,  and  then  very  faintly  indeed.  It  also  became  fainter 
when  traced  toward  the  base. 

The  exact  numbers  in  which  murmurs  were  heard  when 
classified  are  as  follows  : 

Blowing  murmurs  were  heard  in  15  cases. 

In  9  cases  out  of  this  number  the  murmur  was  best  heard 
in  the  fourth  space  on  the  left  side. 

In  6  cases  the  murmur  was  basal. 

In  three  of  the  15  cases  a  murmur  was  heard  in  both  situations . 

In  each  of  these  three  cases  the  cardiac  dullness  was  more 
extensive  than  usual. 


34  ACUTE  DILATATION  OF  THE  HEART 


APPENDIX  C 

.4;/.  analysis  of  150  fatal  cases  of  rheumatic  morbus  cordis  in 
children,  derived  from  the  post-mortem  records  of  the  Hospital 
for  Sick  Children,  Great  Ormond  Street,  and  St.  Mary's 
Hospital. 

The    analysis    contains    observations    upon    the    following 
points  : 

The  sex  incidence  (150  cases). 
The  age  incidence  (150  cases). 

3.  The  number  of  fatal  first  attacks  (115  cases). 

4.  The  relation  of  the  attacks  to  scarlet  fever  (100  cases). 

5.  The  season  in  which  the  fatal  attack  commenced  (150 
cases). 

6.  The  condition  of  the  pericardium  (150  cases). 

(a)  As  to  adhesion. 

(b)  As  to  fluid. 

7.  The  condition  of  the  myocardium  (150  cases). 

8.  The  condition  of  the  mitral  valve  (150  cases). 

9.  The  condition  of  the  aortic  valve  (150  cases). 
to.  The  condition  of  the  tricuspid  valve  (150  cases). 

11.  The  condition  of  the  pulmonary  valve  (100  cases). 

12.  The  combination  of  valvular  lesions  (150  cases). 

13.  The  evidence  of  fresh  rheumatic  manifestations  in  the 
fatal  illness  (150  cases). 

14.  The  frequency  of  nodules  in  fatal  caseb  (8y  cases). 

15.  The  frequency  of  pericardial  friction  toward  the  end  of 
the  illness  (100  cases). 

16.  The  frequency  of  marked  dropsy  (100  cases). 

17.  The  condition  of  the  heart  in  25  cases  with  marked 
dropsy. 

18.  The  frequency  of  sudden  death  as  the  termination  of 
the  illness  (100  cases). 

19.  The  frequency  of  chorea  in  the  last  illness  (100  cases). 

20.  The  condition  of  the  heart  post-mortem  in  fifteen  acute 
attacks  of  rheumatic  fever  rapidly  fatal. 

I.  The  sex  : 

Females    .     .     .     88  =  59  per  cent. 
Males         .     .     .     62  =  41 


IN  CHILDHOOD 


35 


II.  The  age  incidence  : 
Up  to  3^  years  of  age 


4* 

•  »  t2 

»  54 

54 

„  6i 

6-V 

»  7* 

7i 

„  8i 

8i 

»  9^ 

9i 

„  ioi 

oi 

„ni 

ii 

„  12 

i  case 

=  0.6  per  cent 

6  cases 

=  3-9   » 

ii  ,, 

=  7-4   » 

14  » 

=  94   » 

19  » 

=  12.7 

19  » 

=  12.7 

23  » 

=  15-3  „ 

30  „ 

=  20 

18  „ 

=  12 

9  » 

=  6 

150 

The  maximum  is  reached  at  the  tenth  year. 

III.  Fatal  first  attacks. 

It  is  not  always  easy  to  be  certain  that  the  attack  which 
proved  fatal  was  really  the  first  ;  but  out  of  115  fatal  cases 
35  were  apparently  first  attacks. 

IV.  The  relation  (if  any)  to  scarlet  fever. 

Of  100  cases  of  fatal  rheumatism,  in  which  the  occurrence 
or  non-occurrence  of  scarlet  fever  was  noted,  in  only  six  did 
there  seem  to  be  any  possibility  of  a  relation  between  the  two 
diseases.     The  relation  in  these  six  cases  was  as  follows  : 

In  one,  scarlet  fever  occurred  three  years  before,  "  child 
never  well  since." 

In  one,  scarlet  fever  occurred  ten  weeks  before  the  symptoms 
of  rheumatic  fever. 

In  one,  scarlet  fever  occurring  two  years  before  was  at 
once  followed  by  an  attack  of  rheumatic  fever. 

In  one,  scarlet  fever  was  followed  in  a  week  by  rheumatic 
fever. 

In  one,  scarlet  fever  was  followed  in  a  month  by  rheumatic 
fever. 

In  one,  scarlet  fever  was  "  followed  shortly  "  by  rheumatic 
fever.   « 

It  appears,  therefore,  that  rheumatic  fever  in  the  great 
majority  of  cases  arises  quite  apart  from  scarlet  fever. 

V.  The  season  in  which  the  fatal  attack  commenced. 

This   analysis  is   founded  on  the  appearance  of  the   first 


36  ACUTE  DILATATION  OF  THE  HEART 

symptoms  of  the  illness.  This  date  must  be  open  to  some 
doubt,  but  in  a  large  number  of  observations  should  be  fairly 
accurate. 

Of  150  cases  67  commenced  in  the  autumn 


-t  "1 

spring. 

30 

winter. 

20 

summer. 

at  is,  00  per  cent  commenced  in 

autumn  and  spring. 

34 

winter  and  summer 

VI.  The  condition  of  the  pericardium  in  150  cases  : 
(a)  As  to  adhesions  : 

i.     More  or  less  adherent  in  113  —75  per  cent. 
ii.     Not  adherent  in    .  37  =  25 

i.  In  the  cases  (113  in  number)  of  adhesion — 

(a)  In  77  the  adhesion  was  general. 

(b)  In  36  it  was  partial. 

[a)  In  the   77  cases  of  total  adhesion — 

19  were  stated  to  bj  old  adhesions. 
18  „  ,,        recent  adhesions. 

40  were  of  doubtful  age. 

(b)  In  the  36  cases  of  partial  adhesion — 

6  were  described  as  adherent . 
8  ,,  ,,         much  adherent. 

13  „  ,,        partly  adherent, 

g  showed  recent  granular  pericarditis, 
ii.  In  the  ^j  cases  described  as  not  adherent,  in  only  9 
was  the  pericardium  definitely  stated  to  be  healthy. 
(b)  As  to  fluid  in  the  pericardial  cavity  : 
In  38  cases  out  of  150  =  25  per  cent,  a  special  note  was 
made  of  fluid  in  the  pericardial  sac  in  the  following  terms  : 
"  Little  "  or  "  very  little  "     . 
"  Some  "     . 
' '  Under  one  ounce  "     . 
"  Between  one  and  two  ounces  " 
"Between  two  and  three  ounces  ' 
"  Five  ounces  "    . 
"  Six  ounces  " 
' '  Excess  " 
Much  excess 

3& 


111 

9 

cases. 

in 

0 
0 

,, 

in 

4 

,, 

in 

6 

,, 

in 

6 

,, 

111 

1 

case. 

m 

1 

,, 

in 

4 

cases 

111 

4 

,, 

IN  CHILDHOOD 


37 


m 

o   „ 

in 

4   » 

in 

i  case. 

in 

i   „ 

in 

5  cases 

Thus  in  only  12  out  of  150  cases  of  fatal  rheumatic  fever 
is  it  definitely  stated  that  more  than  two  ounces  of  fluid  were 
in  the  pericardial  cavity,  and  in  only  6  cases  more  than  three 
ounces. 

It  is  worthy  of  careful  note  that  much  fluid  in  the  pericardium 
is  rarely  found  after  death  from  rheumatic  pericarditis. 

VII.  The  condition  of  the  myocardium  in  150  cases  : 

(a)  As  to  change  in  appearance,  macrosopic  and  microscopic. 
In  34  cases  there  is  special  mention  of  change — that   is 

in  23  per  cent — in  the  following  terms  : 

"  Soft  and  pale  "  .  .  in  15  cases. 

"  Tough  and  fibroid  " 

"Fatty"     . 

"  Opaque  " 

"  Striae  indistinct  " 

"  Myocardial  change  " 

These  numbers  can  only  be  looked  upon  as  evidence  that 
myocardial  change  occurs.  They  are  no  gauge  of  the  frequency 
of  its  occurrence.  In  many  of  the  cases  microscopic  examina- 
tions of  the  cardiac  walls  were  not  made. 

(b)  The  condition  of  the  myocardium  as  to  hypertrophy 
and  dilatation  in  150  cases. 

Hypertrophy  is  especially  mentioned  in  58  cases  in  the 
following  terms  : 

i.  "Great,"    "much,"   or   "general"   hypertrophy   in    18 
cases.     In  two  of  these  the  left  ventricle  was  especially 
affected, 
ii.  "  Hypertrophy  "  in  29  cases. 

Of  these,  in  7  the  left  ventricle  especially, 
in  1  the  right  ventricle  especially, 
ii.  "  Some  hypertrophy  "  in  8  cases, 
iv.  "  A  little  hypertrophy  "  in  3  cases. 

Dilatation  is  especially  mentioned  in  92  cases.     Thus  : 
i.  "  Marked,"  "  much,"  or  "  general  "  dilatation  in  56, 
Of  these— 

(a)  "  General  dilatation  " 

(b)  "  Marked  "  and  "  much 

(c)  "  Enormous  " 

(d)  "  Great  " 

(e)  "  Of  both  ventricles  " 


m 

19  cases. 

.  in 

24   » 

in 

1  case. 

.  in 

5  cases. 

.  in 

5   „ 

38  ACUTE  DILATATION  OF  THE  HEART 

(f)  "  Of  the  left  ventricle  "    .  .     in    I  case. 

(g)  "  Of  the  right  ventricle  "  .     in    i      ,, 
ii.  "  Dilatation  especially  "  in  4  cases. 

iii.  "  Dilatation  "  in  24  cases. 
iv.  "  Some  dilatation  "  in  6  cases. 
v.  "  Walls  thin  "  in  2  cases. 

In  forming  from  these  data  an  opinion  as  to  the  frequency 
and  relative  amount  of  hypertrophy  and  dilatation  respectively, 
it  must  be  remembered  that  in  some  of  the  cases  no  definite 
statement  is  made  ;  that  in  others  a  preponderance  of  hyper- 
trophy may  have  caused  the  omission  of  any  statement  as  to 
dilatation,  or  vice  vena  ;  finally,  that  the  very  existence  of 
slight  degrees  of  hypertrophy  or  dilatation  may  be  differently 
judged  by  different  observers.  For  these  reasons  the  numbers 
have  not  been  reduced  to  percentages,  but  the  general  tendency 
of  the  facts  recorded  seems  to  indicate  that  dilatation  is  both 
more  frequent  and  more  marked  than  hypertrophy.  For  while 
the  latter  is  noted  in  58  cases  the  former  is  noted  in  92,  and 
in  56  of  these  it  was  evidently  a  striking  fact. 

VIII.  The  condition  of  the  mitral  valve  in  150  cases. 
Affected  in  149. 

The  following  are  the  descriptions  of  the  changes  : 

(1)  '*  Marked  mitral  stenosis  "  in    .  .  9  cases. 

(2)  "  Marked  mitral  regurgitation  "in      .  11 

(3)  "  Much  thickening  and  puckering  "  in         8      ,, 

(4)  "  Mitral  regurgitation  "     1 

"  Mitral  stenosis  "              J-  in    .          .  41      ,, 
"  Double  mitral' '               J 

(5)  "  Some  thickening  "  in                .          .  45      „ 

(6)  "  Numerous  vegetations  "in      .          .  4 

(7)  "  Vegetations  and  small  deposits  "  in  31 

149 

We  may  conclude  that  some  affection  of  the  mitral  valve 
is  almost  invariably  present  in  fatal  rheumatism  in  children  ; 
that  in  about  one  half  of  the  fatal  cases  the  lesion  is  slight, 
in  about  one  fifth  great  ;  that  thickening  of  the  mitral  valve 
is  common,  but  that  a  marked  degree  of  stenosis  is  rare  in 
children  under  twelve. 


39 

n  150  cases. 

The 

1  case. 

4  cases. 

4      V, 

. .     19      „ 

.       18      „ 

5      » 

IN  CHILDHOOD 

IX.  The  condition  of  the  aortic  valves  in  150  cases. 
valve  was  affected  in  51  cases  =  34  per  cent. 

The  details  are  as  follows  : 

(1)  "  Much  aortic  regurgitation  "  in 

(2)  "  Definite  aortic  regurgitation  "  in 

(3)  "  Definite  aortic  stenosis  "in   . 

(4)  "  Vegetations  and  beading  "  in 

(5)  "  Thickening  "in 

(6)  "  Aortic  valves  affected  "in     . 

51 
Slight  change  is  the  rule. 

X.  The  condition  of  the  tricuspid  valve  in  150  cases.  This 
valve  was  affected  in  36  cases  =  24  per  cent. 

The  details  are  as  follows  : 

"  Marked  stenosis  "in  .  .  .         1  case. 

"  Vegetations  "in         .  .  .  .       15  cases. 

"  Thickening  "  in  .  .  .  .        20 

Again,  if  the  valve  is  affected  at  all,  slight  change  is  the  rule. 

XI.  The  condition  of  the  pulmonary  valve  in  100  cases. 
This  was  affected  in  4  =  4  per  cent,  as  follows  : 

"Thickened"    .          .          .          .          .       in  3  cases. 
"  Dilated  " in  1  case. 

XII.  The  frequency  of  a  combination  of  valvular  lesions  in 
149  cases. 

(a)  In  4  cases  at  least  all  the  four  valves  were  affected. 

(b)  In  32  cases  the  mitral,  aortic,  and  tricuspid  valves  were 

affected. 

(c)  In  15  the  mitral  and  aortic  valves  were  affected. 

(d)  In  98  the  mitral  valve  only  was  affected. 

XIII.  The  evidence  of  fresh  rheumatic  manifestations  in 
100  fatal  cases. 

The  evidence  relied  upon  consists  of  chorea,  pericarditis, 
nodules,  arthritis,  and  erythema  occurring  during  the  fatal  illness. 

The  possibility  of  fresh  endocarditis  supervening  upon  old 
is  not  taken  into  account  because  of  the  difficulties  in  proving 
its  occurrence. 

Eighty-six  out  of  100  cases  showed  undoubted  manifesta- 
tions of  recent  rheumatism. 

Of  the  remainder  =  14  per  cent, — 


40  ACUTE  DILATATION  OF  THE  HEART 

Three  cases  were  doubtful. 

Two  cases  died  with  much  cardiac  dilatation. 

One  case  died  with  cerebral  haemorrhage. 

One  case  died,  and  total  adhesion  of  the  pericardium  and 
much  endocarditis  were  found. 

Two  cases  died  with  "  marked  mitral  stenosis." 

Two  cases  died  with  "  marked  mitral  regurgitation." 

Two  cases  died,  and  a  totally  adherent  pericardium  was 
found. 

In  one  case  there  was  a  history  of  three  years'  gradual 
failure. 

These  figures  are  worthy  of  especial  note,  for  they  point 
strongly  to  this  fact,  that  cardiac  break-down  in  children  with 
damaged  hearts  is  mainly  due  to  a  fresh  rheumatic  attack,  not 
to  overstrain. 

XIV.  The  frequency  of  nodules  in  fatal  cases  since  1879. 
Eighty-seven  cases   are  recorded  since  that   date.     In   47 

of  these  nodules  were  present,  and  in  8  their  occurrence  was 
doubtful.  That  is,  nodules  are  found  in  about  54  per  cent  of 
fatal  cases. 

This  result  probably  rather  under-estimates  the  frequency 
of  their  occurrence. 

XV.  The  frequency  of  pericardial  friction  toward  the  end 
of  the  fatal  illness. 

Of  100  cases,  in  55  friction  was  noted,  in  15  it  was  doubtful, 
and  in  30  it  was  not  mentioned. 

XVI.  The  frequency  of  marked  dropsy. 
Observations  are  taken  from  100  cases. 

In  25  cases  it  was  described  as  "  much  "  or  "  considerable." 
In  these  cases — 

(a)  It  was  of  long  standing  in  8  cases. 

(b)  It  was  of  some  standing  in  8  cases. 

(c)  Quite  recent  in  9  cases. 

XVII.  The  condition  of  the  heart  as  found  post-mortem 
in  these  25  cases  of  marked  dropsy. 

Group  A.     The  8    cases  of  long  standing. 

(1)  In  3  there  was  marked  mitral  stenosis. 

(2)  In  1  there  was  thickening  of  the  mitral  valve,  and  the 

pericardium  was  J  of  an  inch  thick. 


IN  CHILDHOOD  41 

(3)  In  1  there  was  mitral  stenosis  and  incompetence   and 

aortic  regurgitation. 
4)  In  1  there  was  marked  mitral  and  tricuspid  incom- 
petence. 
(5)  In  2  mitral  incompetence. 
Group  B.     Eight  cases  of  dropsy  of  some  standing. 

(1)  In  1  there  was  marked  mitral  stenosis. 

(2)  In  3  there  was  marked  mitral  incompetence. 

(3)  In  2  the  heart  was  described  as  fibroid,  and  the  peri- 
cardium was  totally  adherent. 

(4)  In  1  the  chordae  tendineae  of  the  mitral  valve  were 

described  as  much  thickened. 

(5)  In  1  the  pericardium  was  adherent  to  the  chest  wall. 
The  chief  feature  in  these  cases  of  marked  dropsy  is  the 

occurrence  of  decided  valvular  disease. 

XVIII.  The  frequency  of  sudden  death  in  100  cases  ;  by 
this  is  meant  the  occurrence  of  death  unexpectedly  in  the 
last  illness.     This  occurred  in  33  cases,  as  follows  : 

(a)  "  Very  sudden  "  in  n.     In  three  of  these  myocardial 

change  was  noted. 
In  two  of  these  cases  it  is  expressly  stated  that  just  before 
the  sudden  end  the  children  had  been  improving. 

(b)  Attacks  of  collapse  or  much  vomiting,  then  a  sudden 

end,  in  8  cases.  ' 

(c)  "  Sudden  "  in  8  cases. 

(d)  "  Rather  sudden  "  in  6  cases. 

In  many  more  cases  there  was  severe  vomiting  some  days 
before  death. 

XIX.  Fatal  cases  in  which  chorea  was  a  prominent  symptom. 
Some  of  these  cases  had  other  evidences  of  severe  rheumatism 
at  the  time  of  admission,  others  rapidly  developed  them. 
Twenty  cases  are  recorded  here,  and  14  of  these  were  first 
attacks  of  rheumatism. 

This  is  very  striking  confirmation  of  the  close  association 
of  rheumatism  and  chorea — rheumatism,  too,  which  may  prove 
to  be  of  the  most  virulent  type. 

XX.  Brief  abstracts  of  the  post-mortem  appearances  of  the 
heart  in  fifteen  acute  cases  rapidly  fatal. 


42  ACUTE  DILATATION  OF  THE  HEART 

Case  i.  E.  K — ,  aged  n.  Chorea  and  recent  rheumatic 
fever. 

Post-mortem.  The  pericardium  contained  a  considerable 
amount  of  fluid,  with  flakes  of  lymph.  The  heart  weighed 
8^  ounces.  Then-  were  rows  of  bead-like  granulations  on  the 
mitral,  aortic,  and  trier. spid  valves. 

Case  2.  M.  W — ,  aged  9.  Chorea,  first  attack,  and  rheu- 
matic fever. 

Post-mortem.  Recent  granular  pericarditis,  a  little  fluid,  much 
dilatation  of  all  the  cavities,  and  recent  vegetations  on  the 
mitral  and  aortic  valves.     The  heart  muscle  was  flabby. 

Case  3.     G.  K — ,  aged  11.     Acute  rheumatic  fever. 

Post-mortem.  Recent  pericarditis  with  extensive  lymph- 
shreds,  dilatation,  but  very  little  hypertrophy  of  the  ventricle. 
The  mitral  valve  thickened  and  fringed  with  vegetations. 
Minute  vegetations  on  the  aortic  and  tricuspid  flaps. 

Case  4.     F.  S — ,  aged  3.     Acute  rheumatic  fever. 

Post-mortem.  Recent  pericarditis  ;  a  few  drachms  of  fluid 
in  the  sac.  Much  general  dilatation.  The  mitral  valve  dilated, 
with  recent  vegetations  on  the  mitral  and  tricuspid  flaps. 

Case  5.     J.  B — ,  aged  10.     Acute  rheumatic  fever. 

Post  mortem.  Pericarditis  with  much  recent  adhesion  and 
a  little  fluid  ;  fine  aortic  granulations,  and  some  fine  granules 
on  the  mitral  flaps.     All  the  cavities  dilated,  muscle  granular. 

Case  6.     F.  J — ,  aged  4.     Acute  rheumatic  fever. 

Post-mortem.  Recent  pericarditis  ;  a  little  fluid.  Much 
dilatation  of  all  the  cavities.  Some  mitral  thickening  and 
a  few  vegetations  on  the  aortic  valves. 

Case  7.     P.  W — ,  aged  3^.     Acute  rheumatic  fever. 

Post-mortem.  Recent  pericarditis  with  adhesion  ;  one 
ounce  of  fluid  in  the  sac.  Heart  dilated.  Slight  vegetations 
on  the  tricuspid  flaps.    Numerous  fine  vegetations  on  the  mitral. 

Case  8.     M.  M— ,  aged  6£.     Acute  rheumatic  fever. 
Post-mortem.     Recent    general   adhesive   pericarditis.     Two 
drachms  of  fluid  in  the  sac.     General  adhesive  pericarditis. 


IN  CHILDHOOD  43 

General  dilatation  with  a  little  hypertrophy  of  the  left  ven- 
tricle. Some  old  thickening  of  the  mitral  valve.  Slight  aortic 
puckering. 

Case  9.     H.  W — ,  aged  9.     Acute  rheumatic  fever. 

Post-mortem.  Pericarditis,  general,  recent,  and  adhesive. 
Old  vegetations  on  the  mitral,  but  no  stenosis.  The  aortic 
valves  thickened  ;  general  dilatation  of  cavities. 

Case  10.     M.  W — ,  aged  8.     Acute  rheumatic  fever. 

Post-mortem.  General  pericarditis.  Some  fluid  in  the 
pericardial  sac.  Dilatation  of  the  ventricles.  Some  hyper- 
trophy.    Beading  of  the  mitral  valve. 

Case  ii.     C.  S — ,  aged  8.     Rheumatic  fever  and  chorea. 

Post-mortem.  Recent  pericarditis,  general  and  adhesive. 
Small  vegetations  on  the  aortic  and  mitral  valves  ;  heart 
enlarged. 

Case  12.     F.  B — ,  aged  8.     Acute  rheumatic  fever. 
Post-mortem.     Pericardium    totally    adherent  ;     recent    ad- 
hesions.    General  dilatation,  little  valvular  change. 

Case  13.     G.  N — ,  aged  6.     Acute  rheumatic  fever. 

Post-mortem.  The  pericardium  contained  two  ounces  and  a 
half  of  fluid  with  recent  flakes.  Much  dilatation,  and  dilatation 
of  the  valve  orifices.  Little  valvular  change.  Fatty  changes 
in  the  heart  muscle. 

Case  14.     H.  B — ,  aged  11.     Acute  rheumatic  fever. 

Post-mortem.  Pericarditis,  with  recent  adhesions  to  the 
left  ventricle  of  the  heart.  Some  mitral  thickening,  much 
general  dilatation,  and  dilatation  of  the  valve  rings.  Fatty 
changes  in  the  heart  muscle. 

Case  15.     A.  B — ,  aged  n.     Acute  rheumatic  fever. 

Post-mortem.  The  pericardium  contained  one  ounce  and 
a  half  of  fluid.  Some  adhesions,  no  lymph.  Mitral  and 
tricuspid  beading. 


PAPER  NO.   II 

A  CASE  OF  RHEUMATIC  PERICARDITIS  AND 
EXTREME  DILATATION  OF  THE  HEART 

WITH    AX 

INVESTIGATION  INTO  THE  MICROSCOPY 
OF  RHEUMATIC  HEART  DISEASE 

MMUNICATED   BY   Dr.    XORMAX      MOORE 

m  vol.  82  of  the  Medico-Chirurgical  Transactions.) 
1899 

The  facts  determined  in  the  preceding  paper  led  to  an  enquiry  into 
the  pathological  anatomy  of  the  myocardium  in  rheumatic  carditis. 
Some  of  the  results  are  recorded  in  this  paper.  Subsequent  develop- 
ments following  on  the  researches  of  Kent-Hughes,  Aschoff,  Tawara, 
and  others  upon  the  auriculo-ventricular  bundle,  and  the  important 
writings  of  Dr.  James  Mackenzie  -  and  his  pupils  in  this  country, 
and  of  many  others  on  the  Continent,  hare  made  these  results  of 
more  importance  than  we  realised. 

There  will  be  found  in  this  paper  clear  evidence  of  the  focal  nature 
of  the  myocardial  changes,  which  at  this  time  we  fully  appreciated. 
Fig.  No.  2  shows  the  submiliary  nodule,  the  importance  of  which 
and  of  the  cells  contained  within  it  have  been  brought  into  prominence 
by  Aschoff,  Tawara,  and  Carey  Coombs. 

The  pathological  changes  that  are  described  in  this  paper  brought 
further  support  to  the  view  that  acute  rheumatism  was  of  infective 
origin,  but  we  did  not  recognise  at  this  time  the  importance  of  the 
minute  structure  of  the  focal  lesions  or  their  bearing  upon  the  production 
of  cardiac  irregularities. 

This  case,  which  was  under  the  care  of  Dr.  Sidney  Phillips, 
affords  both  clinical  and  pathological  evidence  in  support  of 
the  statements  made  by  Dr.  Lees  and  Dr.  Poynton  in  two  papers 
read  before  this  Society  in  June  1898.  The  first,  by  Dr.  Lees, 
emphasised  the  importance  of  acute  dilatation  of  the  heart  in 
rheumatic  fever  ;  the  second,  a  joint  paper,  dwelt  upon  the 
frequency  of  its  occurrence  in  the  rheumatism  and  chorea  of 
childhood. 

44 


DILATATION  OF  THE  HEART  45 

These  views  were  supported  by  clinical  observations  ex- 
tending over  a  considerable  period  of  time,  and  some  of  the 
results  obtained  were  illustrated  by  cardiac  tracings  thrown 
on  the  screen  by  a  lantern.  Though  personally  assured  of 
the  truth  of  the  clinical  investigation,  they  felt  it  necessary 
to  adduce  pathological  evidence  in  its  support.  This  was  to 
some  extent  supplied  in  an  appendix  to  the  papers,  by  an 
analysis  of  150  cases  of  fatal  rheumatic  fever  in  children  under 
twelve  years  of  age. 

In  the  discussion  that  followed,  the  great  size  of  some  of 
the  cardiac  tracings  was  criticised.  Dr.  Ewart,  accepted  in 
part  the  frequency  of  a  considerable  increase  of  the  precordial 
dullness,  but  considered  the  explanation  to  be  an  evanescent 
pericardial  effusion. 

This  case  is  now  brought  forward  because  it  deals  to  some 
extent  with  these  difficulties,  and  demonstrates  clearly  the 
extreme  dilatation  that  may  occur  in  rheumatic  pericarditis 
with  no  fluid  in  the  pericardium  and  practically  no  valvular 
disease.  The  results  of  the  microscopic  investigations  of  the 
heart,  which  have  been  made  in  this  case,  seem  to  indicate 
clearly  a  morbid  condition  of  its  muscular  structure,  which 
goes  far  to  explain  the  great  dilatation. 

The  case  is  an  example  of  aggravated  cardiac  rheumatism, 
minor  degrees  of  which  are  of  common  occurrence.  There 
will  be,  therefore,  no  need' for  lengthy  clinical  details,  and  those 
facts  which  are  concerned  with  the  condition  of  the  heart  will 
alone  be  described. 

Arthur  G — ,  aged  15,  was  admitted  to  St.  Mary's  Hospital 
on- August  25,  1898,  for  shortness  of  breath.  In  December 
1897,  he  passed  through  an  attack  of  rheumatic  fever  in  which 
several  joints  were  swollen  and  very  painful,  but  for  which 
he  did  not  keep  his  bed.  In  February  1898,  he  had  another 
attack  of  rheumatic  fever,  which  lasted  for  two  months.  Since 
this  last  attack  he  had  suffered  from  occasional  pains  over  the 
heart  on  exertion.  Two  days  previous  to  his  admission  to  the 
hospital  a  small  nodule  appeared  over  the  right  patella. 

On  admission,  on  August  25,  his  temperature  was  ioo°  F., 
pulse  120,  and  respirations  30  ;  he  was  very  pale  and  emaciated. 
The  cardiac  area  was  increased,  the  limits  being  one  finger- 
breadth  to  the  right  of  the  right  sternal  margin,  and  one  and  a 
half  to  the  left  of  the  vertical  nipple  line  ;  upward,  the  limit  was 


46       RHEUMATIC  PERICARDITIS  AND  EXTREME 

the  second  left  intercostal  space.  The  action  of  the  heart  was 
excited,  but  no  pericardial  friction  was  detected.  At  the 
apex  there  was  a  loud,  harsh,  systolic  murmur  conducted 
to  the  axilla,  and  at  the  base  an  accentuated  pulmonary  second 
sound.  The  next  day  pericardial  friction  was  heard,  and  this 
on  the  following  days  became  loud  and  general.  Upon  August 
30  the  area  of  cardiac  dullness  had  increased,  extending  now 
two  finger-breadths  instead  of  one,  to  the  right  of  the  right 
sternal  margin,  and  still  one  and  a  half  beyond  the  left  vertical 
nipple  line.  The  loud  friction  quite  obscured  the  murmur. 
Upon  September  2  the  friction  was  not  so  loud,  but  the  cardiac 
dullness  reached  the  right  nipple  line  and  extended  two  finger- 
breadths  outside  the  left  nipple  line.  Upon  September  3  the 
friction  was  loud  and  general,  and  the  cardiac  dullness  extended 
one  finger-breadth  beyond  the  right  vertical  nipple  line,  and 
about  three  beyond  the  left.  There  was  dullness  in  the  fifth 
right  intercostal  space  (Dr.  Rotch's  sign).  Even  with  the 
greatest  care,  it  was  impossible  to  detect  any  curving  inward 
of  the  right  margin  of  the  cardiac  dullness  at  its  lower  limit. 
Over  the  front  of  the  chest  there  was  doubtful  pleural  friction 
on  both  sides.  Upon  September  7  the  dullness  extended  one 
inch  beyond  the  right  vertical  nipple  line,  and  there  was 
systolic  retraction  of  the  right  intercostal  spaces.  Pericardial 
friction  was  still  well  marked.  The  liver  extended  two  inches 
below  the  costal  margin.  Cough,  vomiting,  restlessness,  and 
all  the  signs  of  acute  cardiac  failure  were  apparent,  and  the 
patient  died  the  following  day.  The  temperature  since  the 
day  of  admission  had  never  risen  above  99. 50. 

The  necropsy  was  made  twenty-four  hours  after  death. 
During  life  the  areas  of  cardiac  dullness  had  been  confirmed 
by  Dr.  A.  G.  Butler,  Dr.  Phillips's  house  physician.  After 
death  the  dullness  was  verified  as  external  to  the  right  nipple, 
and  far  outside  the  left.  This  was  also  confirmed  by  a  post- 
mortem assistant.  Though  the  loud,  general,  and  continuous 
pericardial  friction  did  not  suggest  a  large  effusion,  there  seemed 
every  probability  that  there  would  be  a  distinct  increase  in  the 
amount  of  fluid,  and  the  chest  wall  was  removed  with  especial 
care,  in  order  to  obtain  some  of  this  fluid  in  Pasteur  pipettes 
for  bacteriological  purposes.  The  pericardium  was  however, 
generally  adherent,  and  the  enlargement  almost  entirely  due 
to  the  dilated  heart,  and,  to  a  very  minor  extent,  to  the  thicken- 


., '  ^s 


A  >   -       ,-%*SSv- 


FIG.  1 


FIG. 


Fig.  1.     A  section  through  tin-  pericardium  ami  wall  of  the  left  ventricleof  a  case  of  acute  rheu- 
matic pericarditis.  (a)  Inflamed  pericardium;  (o)  and  (c)  foci  of  cellular  exudation  spreading  from 

the  blood-vessels. 

Fig.  2.     One  of  the  foci  under  high  magnification,     (o)  points  to  the  cellular  exudation  between 
the  muscle-fibres,  now  known  as  the  "Submiliary  Nodule." 


DILATATION  OF  THE  HEART  47 

ing  of  the  pericardium.  The  area  of  dullness  to  the  right  of 
the  sternum  was  due  to  the  greatly  dilated  right  auricle.  In 
front,  over  a  limited  area,  the  pericardial  adhesions  were  firm, 
but  at  the  sides  and  behind  the  adhesions  were  quite  recent, 
and  the  pericardium  in  places  swollen  to  the  thickness  of  half 
an  inch.  The  recent  adhesions  were  in  the  form  of  flakes  of 
lymph,  in  the  interstices  of  which  was  a  little  fluid.  The  two 
lungs  were  pushed  aside  by  the  immense  heart,  and  the  pleurae 
were  adherent  to  the  pericardium  by  recent  adhesions.  The 
valvular  changes  were  extremely  slight,  consisting  only  in 
some  thickening  of  the  mitral  segments  which  did  not  cause 
any  stenosis.  There  was  no  recent  valvular  disease.  The 
valve  rings  were  dilated,  and  the  cavities  of  the  heart  crammed 
with  pale  and  dark  clot,  and  in  the  right  auricular  appendix 
the  clot  was  found  firmly  adherent.  Both  ventricles  seemed 
slightly  hypertrophied.  The  weight  of  the  heart  with  the 
pericardium,  but  empty  of  blood,  was  twenty-six  ounces. 
The  muscle  was  streaked  with  pale  striae,  and  had  on  section  a 
pale  purple  colour.  The  other  viscera  showed  changes  com- 
patible with  a  recent  and  acute  cardiac  failure. 

Numerous  sections  of  the  pericardium,  heart-wall,  blood-clot, 
and  nodules  were  made.  The  salient  points  of  these  will  be 
described.  In  addition,  sections  were  taken  from  other 
examples  of  rheumatic  heart  disease,  from  a  case  of  advanced 
alcoholism,  Addison's  disease,  and  from  a  case  of  cardiac 
fibrosis.  These  appear  to  support  the  views  that  are  held  in 
this  paper,  and  they  will  be  alluded  to  as  the  points  they 
illustrate  are  considered. 

In  the  case  above  described,  a  section  through  the  inflamed 
pericardium  showed  extreme  vascular  dilatation  and  plastic 
inflammatory  exudation  into  the  pericardial  cavity.  In  the 
wall  of  the  left  ventricle  there  was  a  similar  but  slighter  capillary 
distension,  and  both  under  the  pericardium  and  far  away  from 
it  there  was  a  free  exudation  of  small  cells  between  the  muscle- 
fibres.  The  muscle  itself  showed  great  loss  in  striation,  and 
many  of  the  fibres  showed  granules  not  of  a  fatty  nature  in 
the  proximity  of  the  nucleus.  In  sections  through  the  right 
ventricle,  the  most  striking  changes  were  beneath  the  peri- 
cardium, but  they  were  visible  throughout  the  entire  thickness 
of  the  ventricle  wall.  Another  series  of  sections  were  fixed 
in  Hermann's  osmic  fluid.     Both  beneath  the  pericardium  and 


48       RHEUMATIC  PERICARDITIS  AND  EXTREME 

throughout  the  heart-wall  there  was  fatty  degeneration  of  the 
muscle-fibres.  Sections  through  the  right  auricular  appendix 
and  ante-mortem  clot  showed  externally  pericarditis,  then 
hyaline  change  in  the  muscle,  and  coagulation  necrosis  in 
the  blood-clot. 

Thus  it  will  be  seen  that  the  changes  in  the  cardiac  wall  were 
very  general,  affecting  muscle,  vessels,  and  interstitial  tissues. 
The  early  commencement  of  the  interstitial  changes  are, 
however,  better  seen  in  some  sections  taken  from  another 
case  of  pericarditis.  In  this  case,  published  in  the  Lancet,  July 
23.  1898,  death  was  caused  by  a  rare  complication,  extensive 
thrombosis  of  the  large  veins  of  the  neck  and  upper  extremities. 
The  pericardial  friction  in  this  case  was  detected  only  the  day 
before  death.  The  sections  show  numerous  foci  of  inflam- 
matory exudation  scattered  through  the  wall  of  the  ventricle, 
and  were  not  localised  to  that  part  of  the  myocardium  lying 
immediately  beneath  the  pericardium.  In  this  case  also 
during  life  there  was  great  dilatation. 

Though  these  morbid  changes  are  distinct  and  easily  recog- 
nisable, the  parenchymatous  changes  are  by  no  means  as 
profound  in  these  rheumatic  hearts  as  in  some  other  conditions. 
Thus,  in  some  sections  taken  from  the  left  ventricle  of  a  case 
of  advanced  alcoholism,  it  is  difficult  to  recognise  at  first  sight 
the  muscular  tissue,  because  the  changes  are  so  extreme.  Yet 
during  life  it  was  especially  noted  that  there  was  no  appreciable 
dilatation,  a  point  to  which  allusion  will  be  made  later.  Again, 
though  the  alterations  in  the  interstitial  tissues  of  the  heart 
are  quite  definite  in  these  acute  cases  of  rheumatism,  they 
are  more  extreme  in  the  sections  of  a  fibroid  heart  taken  from 
a  case  that  terminated  in  the  sudden  death  of  the  patient. 
Yet  though  the  microscopic  changes  in  these  fatal  cases  of 
acute  rheumatism  were  not  extreme,  they  were  general  and 
diffuse. 

The  sections  next  described  are  also  from  a  case  of  cardiac 
rheumatism,  but  with  a  different  clinical  history.  They  were 
taken  from  the  left  ventricle  of  a  man  aged  twenty-nine.  He 
had  suffered  in  childhood  from  rheumatic  fever,  and  five 
years  before  his  death  had  been  known  to  have  organic, 
mitral,  and  aortic  disease.  He  finally  died  in  another  attack 
of  rheumatism,  complicated  with  pneumonia.  These  sections 
show    fibrosis    of    the   ventricle  —  evidence   of    the    previous 


&np* 


:'# 


FIG.  3 

Rheumatic  myocarditis  showing  fatty  change  in  the  muscular  fibres  in  the  neighbourhood 
of  a  blood  capillary.     The  fat-droplets  are  stained  black  with  osmic  acid. 


FIG.  4 


FIG.  5 


Frc.  4.      A  diagram  of  the  pericardium  and  wall  of  the  left  ventricle.      (a)  Pericardium  : 
(6)  indicates  the  position  in  the  ventricle  from  which  the  sketch  of  the  adjoining'  figure 

was  taken. 
Fig.   5.     (c)  Blood  capillary  cut  longitudinally  ;  (d)  cellular  exudation  between  the  mus- 
cular fibres. 


DILATATION  OF  THE  HEART  49 

rheumatic  attacks,  and  in  addition  multiple  foci  of  small- 
celled  exudation  scattered  through  the  ventricle^evidence 
of  the  recent  illness.  It  is  noteworthy  that  macroscopically 
this  muscle  appeared  natural,  and  that  there  was  not  any 
recent  valvular  disease  or  pericarditis,  but  an  adherent  peri- 
cardium of  old  standing. 

It  remains  now  to  consider  shortly  the  bearing  of  these  details 
upon  the  question  of  rheumatic  dilatation.  The  case  itself 
proves  conclusively  that  great  dilatation,  greater  than  any 
that  was  represented  in  the  tracings  in  the  paper  on  dilatation 
of  the  heart  in  rheumatism,  may  occur  in  rheumatic  fever  with 
plastic  pericarditis,  but  without  valvular  disease  of  any 
appreciable  severity.  It  also  proves  that  Dr.  Rotch's  sign 
may  be  obtained  when  there  is  no  pericardial  effusion.  Such 
a  case  as  this,  taken  together  with  the  previous  clinical  evidence 
makes  it  probable  that  dilatation  of  less  degree  may  occur 
without  pericarditis,  and  that  the  myocardial  changes  are  not 
a  sequela  of  the  pericarditis.  If  pericarditis  is  present  the 
changes  are  concurrent,  and  they  probably  occur  in  the 
myocardium  independently  of  any  pericarditis. 

It  is  usually  considered  that  the  pericarditis  is  the  starting- 
point  of  the  myocardial  inflammation,  and  is  the  explanation 
of  the  dilatation  and  severe  symptoms  that  appear  in  the 
worst  cases  of  cardiac  rheumatism.  Several  observers  have, 
however,  held  that  the  myo-  and  peri-cardial  changes  are  con- 
current, and  part  of  the  same  rheumatic  process.  Thus,  Dr. 
Cheadle,  when  writing  of  chronic  pericarditis,  suggests  this 
in  the  Harveian  Lectures  on  the  "  Rheumatic  State  in  Child- 
hood "  in  1888,  and  the  same  opinion  was  expressed  by  the 
late  Dr.  Sturges  in  the  term  rheumatic  carditis.  Dr.  Theodore 
Fisher,  both  at  the  meeting  of  this  Society  in  June  and  again 
at  Edinburgh  in  July,  stated  that  he  had  observed  pathological 
changes  in  the  myocardium  apart  from  any  pericarditis. 

The  microscopic  sections,  support  the  view  that  when  peri- 
carditis is  present,  the  myocardium  is  also  affected  con- 
currently, for  the  changes  in  the  heart-wall  commence  by 
numerous  Scattered  foci,  some  of  them  far  from  the  pericardium, 
and  the  changes  in  the  muscle  are  general. 

This  view  is  also  supported  by  the  recent  advances  of 
pathology,  especially  in  the  investigation  of  cardiac  muscle, 
for   these  emphasise  the  fact  that  micro-organisms   gaining 

4 


50        RHEUMATIC  PERICARDITIS  AND  EXTREME 

access  to  the  body  give  rise  to  toxines  which  circulate  in  the 
system.  These,  doubtless,  by  delicate  chemical  reactions 
injure  the  tissues,  and  usually  have,  to  some  extent,  a  specific 
action  on  certain  classes  of  tissues.  When  after  death  from 
rheumatic  morbus  cordis,  acute  changes  are  found  throughout 
the  heart,  it  is  most  probable  that  if  rheumatism  be  caused 
by  a  toxine,  these  changes  arose  concurrently  in  a  general 
infection  of  its  structures. 

Allowance,  must  also  probably  be  made  for  the  influence 
of  the  surrounding  tissue  pressures.  The  pericardium,  with 
a  cavity  between  its  two  layers,  and  with  numerous  vessels 
and  lymphatics  lying  in  the  deeper  part  of  its  visceral  portion, 
will,  in  reacting  to  the  rheumatic  poison,  permit  free  exudation 
into  its  sac,  and  after  death  the  result  is  striking  and  at  once 
appreciated.  But  in  the  ventricle  wall  the  firm  and  contracting 
muscle  will  probably  allow  but  little  exudation,  yet  the  morbid 
changes  may  in  the  gravity  of  their  results  be  even  greater. 
After  death  we  may  find  little  macroscopically,  and  when  we 
do  find  changes  we  are  naturally  inclined  to  consider  that 
they  are  less  frequent  in  their  occurrence,  and  commence  after 
the  onset  of  the  pericarditis.  We  have  many  proofs  that  the 
morbid  results  produced  by  a  poison  may  be  extreme,  yet 
the  obvious  morbid  changes  in  the  tissues  themselves  may  be 
slight,  as,  for  example,  in  acute  osteomyelitis  or  in  tetanus. 

Another  point  is  one  upon  which  Dr.  Lees  has  frequently 
laid  stress,  and  to  which  he  recently  called  attention  when 
introducing  the  discussion  upon  rheumatic  heart  disease  in 
childhood  at  the  Edinburgh  meeting  in  July  1898.  It  is 
that  in  rheumatism,  dilatation  is  frequently  very  marked,  yet 
the  clinical  symptoms,  provided  the  patient  be  at  rest,  are 
often  remarkably  slight. 

At  first  sight  this  is  difficult  to  realise,  but  the  explanation 
probably  lies  in  the  fact  that,  the  function  of  the  cardiac 
muscle  is  damaged  in  a  peculiar  way  rather  than  destroyed 
by  the  rheumatic  poison. 

A  tissue  so  complex  as  the  cardiac  muscle  is  liable  to  a 
variety  of  pathological  changes,  and  these  probably  have  a 
different  morbid  significance.  Some  of  these  changes  may 
be  far  more  detrimental  to  the  vital  properties  of  the  muscle 
than  others.  Those  that  are  the  most  destructive  may  cause 
death  from  syncope  without  appreciable  dilatation,  as  occurred 


?^rar&&°fr. 


••••:/.  "•^^#£i^:^  ■■■■.  •■  >^<* 


TT^W 


FIG.  6 


Section   of   left   ventricle    from   a   case   of   recurrent   rheumatism, 
Bhowing  extensive  perivascular  fibrosis. 


FIG.  7 

Section    from    the  left   ventricle  of  a   man  aged  30,  the  victim   of 
rheumatic  Eever  in  childhood,  showing  extensive  fibrosis. 


DILATATION  OF  THE  HEART  51 

in  the  case  of  alcoholism  referred  to  above,  and  also  in  the 
case  of  Addison's  disease.  Those  changes  which  are  less 
destructive  may  cause  perversion  or  impairment  of  function, 
ending  perhaps  in  death,  but  with  great  dilatation  of  the  heart 
during  life. 

Clinically,  the  first  definite  evidence  of  advanced  fatty 
degeneration  of  the  heart  may  be  sudden  death  ;  and  so  we 
may  expect  that  in  rheumatism,  with  morbid  changes  of  a 
less  severe  type,  the  symptoms  due  to  the  dilatation  may 
be  but  slightly  marked. 

It  is,  also  perhaps  legitimate  to  consider  what  would  have 
happened  had  the  case  recorded  in  this  paper  made  a  tem- 
porary recovery.  The  pericardium,  we  know,  would  have 
become  less  hyper aemic,  have  shrunk,  and  finally  have  become 
generally  adherent.  It  is  more  difficult  to  follow  the  fate  of 
the  muscle,  but  probably  much  would  have  been  replaced  by 
fibrous  tissue.  The  sections  through  the  ventricle  of  the  case 
of  recurrent  rheumatism  support  this  view.  If  the  boy  had 
then  died  in  a  relapse,  twelve  months  later/there  would  have 
been  a  temptation  to  lay  much  stress  upon  the  mechanical 
effect  of  the  obvious  adherent  pericardium,  and  little  upon 
the  loss  of  vital  power  due  to  the  damaged  muscle. 

Finally,  in  rheumatic  children  it  is  certain  that  it  is  the  active 
rheumatism  that  usually  kills.  It  is  very  probable  that  in 
adults  also  active  rheumatism  is  of  more  importance  than 
might  be  thought  ;  and  that  the  explanation  of  some  cases  of 
organic  heart  disease,  which  fail  to  react  to  treatment,  and  in 
which  the  symptoms  far  outweigh  the  clinical  signs,  is  not  the 
adherent  pericardium  so  often  found  after  death,  but  this  active 
rheumatism  injuring  the  cardiac  muscle.  The  evidences  of 
this  rheumatism  may  be  slight,  and  possibly  we  do  not  even 
yet  fully  recognise  its  manifestations.  It  is  interesting  that 
not  infrequently  there  is  in  these  unfavourable  cases  a  history 
of  recent  rheumatism,  and  now  and  again  such  definite 
symptoms  as  arthritis  develop  during  their  stay  in  hospital. 
These  symptoms  could  then  hardly  be  due  to  a  fresh  infection, 
and  are  more  probably  an  evidence  of  active  rheumatism 
which  had  existed  from  the  time  that  the  cardiac  breakdown 
brought  them  to  the  hospital. 

Since  this  paper  was  communicated  in  February,  microscopic 
sections  of  the  cardiac  muscle  have  been  obtained  in  three 


52  RHEUMATIC  PERICARDITIS 

more  cases,  each  of  which  show  changes  that  bear  upon  the 
question  considered  in  this  paper.  Dr.  Cheadle,  Dr.  Lees, 
and  Dr.  Phillips  have  kindly  given  leave  to  give  a  brief  outline 
of  their  histories. 

Dr.  Cheadle 's  case  was  that  of  a  man  of  thirty,  who  had 
suffered  from  rheumatic  fever  in  childhood,  and  was  admitted 
for  aortic  and  mitral  incompetence.  The  symptoms  were 
most  urgent,  quite  overshadowing  the  physical  signs.  The 
sections  of  the  left  ventricle  showed  much  fibrosis. 

Dr.  Lees'  case,  that  of  a  girl  of  eighteen,  was  one  of  acute 
carditis,  almost  precisely  similar  to  the  case  recorded,  but  even 
more  convincing  because  there  was  no  marked  thickening  of 
the  pericardium.  The  fatty  changes  throughout  the  heart- 
wall  were  remarkable. 

Dr.  Phillips'  case  was  that  of  a  woman  of  twenty-three,  who 
died  of  "infective  endocarditis,"  probably  of  rheumatic 
origin.  There  were  mural  vegetations  upon  the  endocardium 
of  the  left  ventricle.  The  ventricle-wall  showed  acute  in- 
flammatory changes,  but  the  pericardium  was  completely 
adherent  from  a  previous  rheumatic  attack. 


PAPER  NO.   Ill 

A    STUDY    OF    THE    HEART-WALL    IN 

DIPHTHERIA,  RHEUMATIC  FEVER, 

AND  CHOREA 

(Reprinted  from  the  Lancet,  May  12,  1900.) 

The  preceding  papers  having  established  the  reality  and  importance 
of  myocardial  changes  in  rheumatism,  in  this  one  they  are  compared 
with  those  produced  by  undoubted  infections,  such  as  the  diphtheritic  and 
staphylococcic.  The  result  is  to  strengthen  the  view  that  these  myo- 
cardial changes  in  rheumatism  are  the  result  of  an  infective  process. 
The  changes  described  in  the  heart  in  the  case  of  chorea  provide  a  link 
in  the  chain  of  evidence  establishing  the  rheumatic  origin  of  this 
manifestation. 

The  results  which  are  produced  in  the  heart  by  diphtheria 
and  rheumatic  fever  respectively  appear  at  first  sight  to  be 
so  different  that  to  compare  them  might  seem  to  be  of  doubtful 
value.  Diphtheria  recalls  the  sudden  catstrophe  of  death 
from  syncope  and  a  heart  the  valves  and  pericardium  of 
which  are  unaffected.  Rheumatic  fever,  on  the  other  hand, 
recalls  a  prolonged  illness — a  series  of  partial  victories  and 
defeats — associated  pathologically  with  valvular  and  peri- 
cardial inflammation  and  clinically  with  valvular  murmurs 
and  pericardial  friction  sounds.  Nevertheless,  it  is  well  known 
that  diphtheria  very  frequently  injures  the  heart  in  a  way  that 
differs  from  this  dramatic  nerve  paralysis  and  syncope  by 
acting  as  a  direct  poison  to  the  cardiac  muscle.  The  proof 
of  this  rests  not  only  upon  clinical  and  pathological  evidence 
but  upon  the  evidence  of  experimental  pathology.  Quite 
recently  this  action  of  the  diphtheria  toxins  upon  the  heart 
has  been  emphasised  by  Dr.  Villy,  late  assistant  medical 
officer  to  the  Park  Fever  Hospital,  in  a  paper  upon  vomiting 
and  cardiac  failure  in  this  disease.1  There  is  in  this  form  of 
cardiac  affection  dilatation  of  the  heart  (which  is  usually 
moderate),  feebleness  of  the  pulse,  and  disturbance  of  rhythm. 

53 


54  THE  HEART-WALL  IN  DIPHTHERIA 

The  first  sound  at  the  apex  is  short,  and  the  pulmonary  second 
sound  becomes  unduly  loud  ;  in  severe  cases  the  patient  lies 
in  bed  pale  and  quiet  with  the  muscle  devoid  of  tone  and  the 
mind  listless.  The  condition  is  one  that  may  be  seen  early  in 
the  disease  and  may  occur  without  any  symptoms  of  nerve 
paralysis.  In  rheumatic  fever,  also,  there  may  be  dilatation 
of  the  heart  which  is  sometimes  considerable,  and  this  may 
occur  irrespectively  of  demonstrable  valvular  or  pericardial 
inflammation.  With  this  dilatation  there  are  feebleness  of 
the  pulse,  shortness  of  the  first  sound,  and  accentuation  of  the 
pulmonary  second  sound.  There  are  also,  to  a  minor  degree, 
pallor,  listlessness,  and  loss  of  muscular  tone.  The  explana- 
tion of  this  condition  in  rheumatism  is  in  all  probability  that 
the  poison  of  the  disease  has  also  a  direct  effect  upon  the 
cardiac  muscle. 

In  this  paper  evidence  is  brought  forward  in  support  of 
this  view,  and  the  argument  is  based  upon  the  results  of  clinical 
observation  and  microscopical  investigation  of  the  heart-wall. 
These  investigations,  extending  over  three  years,  include 
observations  upon  18  cases  of  rheumatic  heart  disease,  four 
cases  of  diphtheria,  a  case  of  chorea,  and  a  case  of  septicaemia 
in  an  animal  injected  with  a  pure  culture  of  staphylococci. 
One  of  the  cases  of  diphtheria,  one  of  the  cases  of  rheumatism, 
and  the  case  of  chorea  are  selected  from  these  to  illustrate  the 
salient  points  in  this  argument.  For  the  sake  of  clearness  a 
brief  allusion  will  first  be  made  to  the  clinical  course  of  the 
cases  of  diphtheria  and  rheumatism.  The  details  of  the 
microscopy  are  dealt  with  at  greater  length  and  the  extreme 
changes  in  the  heart-wall  in  these  two  examples  are  represented 
in  the  drawings  from  the  sections  of  the  myocardium. 

Case  i.  The  case  of  diphtheria.  The  patient,  a  child, 
about  five  years  of  age,  contracted  a  sore-throat  which  developed 
the  characters  of  faucial  diphtheria.  Later  in  the  illness  signs 
of  progressive  and  grave  cardiac  failure  became  evident.  The 
pulse  was  extremely  feeble  and  there  were  pallor,  vomiting, 
restlessness,  and  finally  almost  complete  suppression  of  urine. 
There  was  no  evidence  of  diphtheritic  neuritis,  and  the  child 
died  from  cardiac  failure  on  the  seventeenth  day  of  the  illness. 

Dr.  John  Morton  made  a  necropsy  within  24  hours  of  death 
and  brought  us  for  examination  parts  of  the  left  ventricle  and 


RHEUMATIC  FEVER  AND  CHOREA      55 

kidneys.  The  kidneys  showed  extreme  congestion  but  no 
indication  of  an  acute  nephritis.  The  condition  of  the  myo- 
cardium was  as  follows  :  The  Macroscopic  changes.  The 
cardiac  muscle  was  pale  and  the  pericardium  was  normal.  The 
Microscopic  changes.  Fixative  Hermann's  fluid.  Stain 
safranin. 

1.  In  the  muscle  fibres.  Transverse  striation  was  lost  in 
many  places,  but  was  still  present  in  others.  In  some  fibres 
longitudinal  striation  was  more  evident  than  usual.  The 
contour  of  many  of  the  fibres  was  irregular  and  the  irregularity 
was  due  in  part  to  shrinking  in  width  from  destruction,  and  in 
part  to  bulging  from  fatty  changes.  Some  of  the  fat  droplets 
were  of  considerable  size,  and  the  areas  in  which  the  fatty 
changes  in  the  fibres  were  marked  were,  as  is  usual  in  diphtheria, 
very  irregular  in  distribution.  Some  of  the  fibres  were  com- 
pletely destroyed  and  the  field  of  section  had  in  these  places  a 
reticular  structure.  Transverse  sections  of  the  muscle  fibre 
showed  the  variability  in  their  size  with  great  distinctness. 

2.  In  the  nuclei.  The  nuclei  of  the  muscle  fibres  showed 
great  variability  in  size  and  staining  properties.  In  some 
fibres  the  nuclei  were  swollen,  in  many  divided  into  two,  and 
in  some  of  these  a  few  dark  granules  could  be  seen  between 
the  two  nuclei.  Some  of  the  swollen  nuclei  stained  diffusely 
and  exemplified  very  clearly  the  condition  of  hyperchromatosis. 
The  granules  that  were  present  in  the  space  between  the 
divided  nuclei  stained  with  the  methyl  green,  and  did  not, 
as  is  the  rule  in  more  chronic  affections  of  the  heart,  show  that 
dark-brown  colouration  which  is  so  characteristic  an  appearance 
in  this  tissue.  Other  nuclei  were  very  small  and  also  stained  a 
diffuse  green.  Some  were  round  in  outline  and  appeared  as 
mere  dots  in  the  centre  of  the  fibre.  In  some  the  chromatin 
network  was  definite  and  evenly  distributed  ;  in  others  it  was 
massed  to  the  poles,  leaving  a  colourless  centre  ;  and  in  others 
it  was  centric,  leaving  a  colourless  periphery.  In  many  cases 
the  protoplasm  of  the  muscle  fibre  in  the  neighbourhood  of  the 
nuclei  showed  an  appearance  of  vacuolisation. 

3.  In  the  interstitial  tissue.  Some  portions  of  the  left 
ventricle  were  fixed  in  perchloride  of  mercury  and  the  sections 
showed  that  there  was  no  increase  in  the  fibrous  tissue  of  the 
ventricle  wall,  but  in  places  there  was  an  increase  in  the  cellular 
elements  between  the  fibres. 


56  THE  HEART-WALL  IN  DIPTHERIA 

4.  In  the  pericardium.     The  pericardium  was  not  inflamed. 

There  was,  then,  in  this  case  a  severe  destructive  lesion  of 
the  essential  elements  of  the  heart-wall  such  as  has  been 
recorded  by  many  'other  observers  in  this  form  of  diphtheritic 
heart  failure. 

At  this  point  it  is  necessary  to  make  a  brief  allusion  to  the 
microscopic  investigations  of  the  heart-wall  in  animals  that 
have  been  injected  with  diphtheria  toxins.  This  work  has 
been  carried  out  by  various  experimental  pathologists  and 
an  allusion  must  be  made  to  a  paper  by  Mollet  and  Regaud 
upon  the  subject.2  These  observers  found  that  lesions  of  the 
muscular  fibres  were  constant  and  that  they  occurred  some- 
times alone  and  sometimes  together  with  an  interstitial 
leucocytosis.  Vascular  lesions  in  the  myocardium  also  were 
frequent.  Macroscopically  there  were  in  some  cases  endo- 
cardial, myocardial,  and  pericardial  haemorrhages,  and  an 
abnormal  appearance  of  the  myocardium  was  frequent.  (1)  In 
the  muscle  fibre  under  the  microscope.  There  were  granular 
and  fatty  changes  in  the  muscle  fibres  and  sometimes  vacuolisa- 
tion.  Striation  was  often  lost.  (2)  In  the  nuclei.  The 
nuclei  were  found  distorted,  swollen,  and  stained  with  difficulty. 
(3)  In  the  interstitial  tissues..  There  was  in  some  cases  an 
increase  of  the  cellular  elements  between  the  fibres.  More 
details  were  given  in  this  paper  as  to  the  date  of  appearance 
and  probable  meaning  of  these  abnormalities,  but  it  is  sufficient 
for  the  present  purpose  to  recognise  the  similarity  of  these 
changes  to  those  described  in  the  case  of  diphtheria. 

Case  2.  The  case  of  rheumatism.  A  young  man,  aged 
19  years,  was  admitted  into  St.  Mary's  Hospital  on  December  4, 
1899,  for  pains  in  the  limbs  and  morbus  cordis.  There  was  a 
history  of  three  previous  attacks  of  rheumatic  fever,  the  first 
occurring  at  the  age  of  seven  years.  Whe  1  admitted  the 
patient  was  very  ill,  the  face  was  cyanosed,  and  there  was 
orthopneea.  The  temperature  was  1020  F.,  the  pulse  was  108, 
and  the  respirations  were  40.  The  pulse  was  feeble  and  the 
heart  was  excited  and  greatly  dilated.  There  was  some  chronic 
mitral  disease.  Pleural  friction  was  audible  on  both  side, 
but  we  did  not  detect  pericardial  friction  at  the  time  of  his 
admission.  The  next  day  there  was  general  pericardial 
friction,  and  death  rapidly  followed  on  the  7th. 

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RHEUMATIC  FEVER  AND  CHOREA      57 

ounces  of  slightly  turbid  fluid  were  found  in  the  pericardial 
sac,  with  some  recent  lymph  especially  upon  the  posterior 
aspect  of  the  heart.  There  was  no  great  distension  of  the 
pericardial  sac  with  this  fluid  and  by  no  means  sufficient  to 
account  for  the  wide  cardiac  area  during  life.  The  appearance 
of  the  heart-wall  was  remarkable  for  its  great  pallor.  The 
mitral  valve  showed  no  recent  changes  but  those  of  a  moderate 
stenosis  due  to  previous  fibrosis.  The  aortic  valve  showed 
recent  vegetations  springing  from  previously  uninjured  cusps. 
The  valves  on  the  right  side  were  unaffected. 

In  the  muscle  fibres  under  the  microscope.  The  striking  feature 
was  the  extreme  fatty  change,  some  of  these  being  almost  a 
mass  of  fine  fat  droplets.  This  change  extended  through  the 
ventricle  wall  and  was  remarkably  general.  In  some  cases, 
nevertheless,  a  considerable  number  of  fibres  had  escaped  that 
change  and  showed  distinct  striation.  The  contour  of  the 
fibres  was  preserved  and  that  extent  of  destruction  seen  in  the 
case  of  diphtheria  was  absent. 

Under  higher  magnification.  Stained  by  methyl  green. 
The  nuclei  showed  well  and  their  size  was  fairly  constant. 
Marked  alteration  of  shape  and  staining  properties  were  not 
as  evident  as  in  the  case  of  diphtheria.  Under  this  high 
magnification  minute  clear  spaces  could  be  seen  in  the  muscular 
fibres  in  addition  to  the  fatty  change. 

There  was  some  cell  exudation  between  the  muscle  fibres  in 
the  neighbourhood  of  the  vessels  lying  in  the  interstitial  tissue. 

The  pericardium  showed  recent  inflammatory  change,  the 
endothelial  lining  still  remaining  intact.  There  was  no 
evidence  of  a  previous  pericarditis. 

To  summarise  :  there  was  disease  of  the  muscular  fibres, 
but  the  destructive  nature  of  the  change  was  not  of  the  same 
gravity  as  in  the  case  of  diphtheria,  and  it  is  probable  that 
these  changes  were  due  to  the  direct  action  of  the  rheumatic 
poison  upon  the  myocardium.  At  this  point  a  difficulty 
arises,  for  in  rheumatism  as  yet  no  specific  organism  has  been 
generally  admitted  and  no  toxins  can  be  measured  out  by 
pathologists  for  inoculation  experiments  upon  animals.  There 
are  no  investigations  to  be  put  side  by  side  with  those  of  Mollet 
and  Regaud  to  which  reference  has  been  made  and  to  argue 
that  because  the  changes  found  in  the  heart-wall  in  rheumatism 
and  diphtheria  are  very  similar  it  follows  that  they  are  neces- 


58  THE  HEART-WALL  IX  DIPHTHERIA 

sarily  due  to  a  direct  action  of  their  poisons  may  seem  hazardous 
since  rheumatism  and  diphtheria  are  widely  different  diseases. 

Between  rheumatism  and  septic  infections  there  is  a  closer 
link,  and  a  brief  reference  is  now  made  to  an  investigation 
of  the  cardiac  wall  from  a  rabbit  that  had  died  from  septicaemia 
caused  by  an  inoculation  of  a  pure  culture  of  staphylococci. 
The  animal  died  on  the  sixth  day  after  the  injection  of  staphy- 
lococci. The  kidneys  were  full  of  small  pyaemic  abscesses, 
and  in  the  heart-wall  between  the  muscle  fibres  were  foci 
of  inflammatory  exudation  containing  staphylococci.  The 
cardiac  muscle  showed  definite  fatty  change,  patchy  in  dis- 
tribution. In  a  paper  upon  venous  thrombosis  in  rheumatic 
fever  (1898)  3  and  in  papers  read  before  the  Royal  Medical  and 
Chirurgical  Society  and  at  the  Portsmouth  meeting  of  the 
British  Medical  Association  4  in  1899,  allusion  was  made  to 
similar  inflammatory  foci  in  rheumatic  fever.  The  close 
relation  that  rheumatism  bears  to  septic  infections  is  un- 
doubted, and  this  observation  is  of  value  because  it  is  an 
evidence  that  fatty  changes  in  the  heart  muscle  are  not 
necessarily  the  result  of  prolonged  impairment  of  the  cardiac 
circulation.  It  is  of  interest,  also,  because  it  appears  to  throw 
some  light  upon  the  morbid  anatomy  of  the  third  case — the 
case  of  chorea. 

Case  3.  The  case  of  chorea.  This  case  was  an  example  of 
that  type  of  chorea  in  which  the  movements  are  extremely 
violent,  and  death  is  not  associated  with  gross  cardiac  in- 
flammation. The  heart  after  death  showed  only  a  slight 
inflammation  of  the  mitral  valve.  Microscopical  investigation 
showed  numerous  micro-organisms  in  the  valve  and  in  the 
vessels  at  the  base  of  the  valve.  Many  sections  of  the  left 
ventricle  were  examined  and  some  distinct  foci  of  inflammatory 
exudation  were  found  comparable  to  those  which  may  be 
found  in  acute  rheumatism  or  more  obviously  in  the  acute 
pyaemia  from  the  injection  of  staphylococci  into  the  circula- 
tion. In  addition  there  was  early  fatty  change  in  some  of 
the  muscle  fibres,  patchy  in  distribution.  The  close  resem- 
blance between  this  condition  and  that  found  in  the  rabbit's 
heart  is  suggestive,  and  both  appear  to  us  to  strengthen  the 
probability  that  rheumatism  directly  injures  the  cardiac  wall. 

To  return  once  more  to  the  case  of  rheumatic  fever.  A 
brief  analysis   of   this  case   furnishes   additional   evidence  in 


RHEUMATIC  FEVER  AND  CHOREA      59 

favour  of  the  myocardial  change  being  due  to  the  direct  action 
of  the  poison  upon  the  muscle.  The  importance  of  the  case 
lies  especially  in  the  fact  that  the  pericarditis  was  a  terminal 
event  in  the  disease,  and  that  the  pericardium  had  not  been 
attacked  in  the  previous  rheumatic  outbreaks.  When  the 
patient  was  first  admitted  there  was  no  pericardial  friction, 
though  the  illness  had  extended  over  at  least  four  weeks  and 
the  heart  was  greatly  dilated.  This  absence  of  pericardial 
friction  was  no  complete  proof  of  the  absence  of  pericarditis, 
but  after  death  recent  flakes  of  lymph  and  a  considerable 
quantity  of  slightly  turbid  fluid  were  found  in  the  pericardial 
sac — a  sure  indication  of  an  acute  rheumatic  inflammation 
of  brief  duration.  If,  then,  the  clinical  and  pathological 
facts  are  coupled  together  there  can  be  no  doubt  that  in  this 
case  the  pericarditis  was  a  terminal  event.  The  extreme 
myocardial  disease  cannot,  therefore,  be  explained  as  secondary 
to  pericarditis,  and  no  one  would  maintain  that  it  was  the 
result  of  a  comparatively  slight  valvular  lesion.  It  is  most 
probably  to  be  explained  as  the  direct  effect  of  the  rheumatic 
poison.  This  view  is  also  supported  by  the  finding  of  similar 
myocardial  disease  in  four  other  acute  cases  of  rheumatic 
fever,  two  of  which  have  already  been  published.5 

The  practical  bearing  of  this  view  is  very  considerable.  It 
emphasises  the  important  part  that  active  rheumatism  takes 
in  the  history  of  rheumatic  morbus  cordis.  It  is  realised 
that  in  children  active  rheumatism  is  of  vital  importance,  a 
fact  further  borne  out  by  the  analysis  of  fatal  cases  of  rheumatic 
fever  in  children  under  12  years  of  age.6  In  adults  the  occur- 
rence is  more  liable  to  be  overlooked.  The  condition  of  chronic 
rheumatic  morbus  cordis  with  the  secondary  changes  that 
result  from  previous  valvular  inflammation  is  apt  to  be  raised 
to  the  position  of  a  primary  disease  rather  than  to  be  classed 
as  a  symptomatic  affection  and  the  breakdown  to  be  sought 
for  in  mechanical  overstrain.  Yet  in  adults,  as  in  children, 
fleeting  rheumatic  pains  in  the  joints  and  pleuritic  and  prae- 
cordiarpains  are  all  frequent  at  the  time  when  the  heart  gives 
way.  It  may  be  safely  asserted  that  if  a  children's  hospital 
is  full  of  cases  of  active  rheumatism  and  chorea  an  adult 
hospital  will  be  full  of  broken-down  chronic  heart  disease  of 
rheumatic  origin.  After  death  in  these  chronic  cases  recent 
granulations  may  be  found  on  the  valves  without  any  clinical 


60  THE  HEART-WALL  IN  DIPHTHERIA 

evidence  of  rheumatism  to  lead  to  a  suspicion  of  the  active 
process — a  point  to  which  Dr.  A.  Garrod  has  also  called 
especial  attention  at  the  recent  discussion  on  rheumatism  at 
the  Chelsea  Clinical  Society.  It  is  difficult  in  these  complex 
cases  to  point  with  certainty  to  myocardial  failure  as  the  cause 
of  the  cardiac  breakdown  ;  for  there  is  no  myocardial  friction 
sound  or  bruit  to  clinch  the  diagnosis.  The  results  have  to 
be  judged  often  enough  by  symptoms  which  may  be  almost 
as  well  explained  on  the  hypothesis  of  a  mechanical  failure. 
Yet  the  point  is  one  of  importance,  for  if  due  to  rheumatic 
affection  of  the  myocardium  the  power  of  the  heart  is  under- 
mined at  its  very  foundation. 

Another  practical  point,  perhaps  the  most  important  of  all, 
concerns  the  first  attacks  of  rheumatism  that  are  met  with 
most  frequently  in  childhood.  The  myocardium  may  show 
signs  of  the  rheumatic  disease  before  the  valves  or  pericardium,7 
and  no  clinical  fact  is  more  striking  than  the  unobtrusive 
method  in  which  rheumatism  produces  in  childhood  heart 
disease  which  is  often  incurable.  In  such  cases  as  these, 
to  wait  for  a  definite  systolic  valvular  murmur  before  deciding 
that  the  heart  is  affected  is  dangerously  akin  to  awaiting 
faecal  vomiting  for  a  proof  of . intestinal  obstruction.  If  the 
development  of  incurable  rheumatic  heart  disease  is  to  be 
satisfactorily  arrested  the  best  opportunity  will  be  before 
definite  proof  of  its  existence  is  demonstrable  by  a  valvular 
murmur. 

A  study  of  the  microscopical  details  of  the  myocardial 
changes  in  diphtheria  and  rheumatism  explains  possibly  the 
clinical  fact  that  the  dilatation  in  diphtheria  is  usually  not  so 
marked  as  in  rheumatism,  but  the  tendency  to  a  fatal  termina- 
tion is  vastly  greater.  The  poison  of  diphtheria  appears  to 
destroy  the  muscle  fibres  far  more  than  does  that  of  rheu- 
matism. The  drawings  in  this  paper,  made  under  a  compara- 
tively low  power,  are  sufficient  to  illustrate  this  point.  This 
is,  a  warning  not  to  raise  dilatation  of  the  heart — a  clinical 
entity  so  definite  and  well  recognised — into  the  position  of  a 
primary  disease,  for  if  this  be  done  it  is  natural  enough  to 
consider  that  the  greater  the  dilatation  the  greater  the  danger. 
Yet  the  truth  of  this,  even  for  any  one  disease,  is  only  approxi- 
mate, for  all  diseases  vary  in  their  virulence  and  individual 
effects,  and  those  that  attack  the  cardiac  wall  may  damage  the 


RHEUMATIC  FEVER  AND  CHOREA      61 

muscle  fibre  at  one  time  far  more  than  at  another.  A  poison 
acting  upon  the  myocardium  with  great  virulence,  will,  it  is 
clear,  cause  such  an  impairment  of  the  heart's  force  that  death 
must  occur  before  there  is  marked  dilatation,  an  occurrence 
not  infrequent  in  diphtheria.  It  is  probable  that  in  rheumatism 
also  this  question  of  greater  or  less  virulence  is  an  important 
one.  Though  the  extent  of  the  cardiac  dilatation  must 
necessarily  be  a  sign  of  very  great  significance,  it  is  in  these 
myocardial  affections  that  the  paramount  importance  of  the 
symptoms  becomes  apparent  ;  for  these  symptoms,  we  should 
suppose,  even  more  than  the  dilatation,  are  an  index  of  the 
muscle  failure.  In  this  principle  probably  lies  the  explanation 
of  some  of  those  more  obscure  cases  of  cardiac  rheumatism, 
cases  in  which,  without  evidence  of  valvular  or  pericardial 
disease,  there  remain  unaccountable  breathlessness,  precordial 
pain,  and  other  indications  of  cardiac  inadequacy.  Finally, 
from  the  theoretical  standpoint  the  changes  in  the  cardiac 
wall  in  acute  rheumatism  are  of  interest  because  their  nature 
and  complexity  are  decided  evidence  in  favour  of  rheumatic 
fever  being  due  to  a  microbic  infection.  In  this  paper  it 
may  be  pointed  out  that  the  view  that  the  poison  of  rheumatism 
acts  directly  upon  the  muscle  does  not  imply  that  this  poison 
is  necessarily  the  result  of  a  microbic  infection,  though,  short  of 
absolute  proof,  the  infectious  origin  of  rheumatic  fever  appears 
to  rest  upon  very  strong  evidence. 

In  conclusion,  our  thanks  are  again  due  to  Mr.  H.  G.  Plimmer, 
pathologist  to  the  hospital,  for  invaluable  advice  as  to  technique 
and  methods  of  investigation  whilst  working  in  the  laboratory 
at  St.  Mary's  Hospital. 

REFERENCES 

1  "  Vomiting  and  Cardiac  Failure  in  Connection  with  Diphtheria, 
Medical  Chronicle,  September  1899. 

2  "  Myocardite  Diphtherique,"  Annates  de  I'Institut  Pasteur,  No.  2, 
25  Fevrier  1897. 

3  "Three  Cases  of  Extensive  Venous  Thrombosis  associated  with 
Severe  Rheumatic  Carditis,"  the  Lancet,  July  23,  1898,  p.  206.  Paper 
No.  VI.  * 

4  "  Rheumatic  Pericarditis,  with  an  Investigation  into  the  Micro- 
scopy of  Rheumatic  Morbus  Cordis,  Transactions  of  the  Royal  Medical 
and  Chirurgical  Society,  1899.  "  Some  Observations  upon  the  Patho- 
logy of  the  Myocardium,"  Brit.  Med.  Jour.,  November  1899.  Papers 
Nos.  II  and  IV. 


62  THE  HEART-WALL  IN  DIPHTHERIA 

5  "  A  Case  of  Virulent  Acute  Rheumatism  with  Extensive  Purpura," 
the  Lancet,  October  28,  1890,  p.  1163.    Paper  No.  VII. 

6  Lees  and  Poynton,  "  An  Analysis  of  150  Fatal  Cases  of  Rheuma- 
tism in  Children  under  12  Years  of  Age,"  Transactions  of  the  Royal 
Medical  and  Chirurgical  Society,  i8q8.    Paper  No.  I. 

7  Lees  and  Povnton.  "  Acute  Dilatation  of  the  Heart  in  the  Chorea 
and  Rheumatism  of  Childhood,"  Transactions  of  the  Royal  Medical 
and  Chirurgical  Society,  1SS8.    Paper  No.  I. 


PAPER  NO.   IV 

OBSERVATIONS   UPON   THE   PATHOLOGY   OF 
THE  MYOCARDIUM 

(Reprinted  from  the  British  Medical  Journal,  November  4,  1899.) 

This  paper,  while  to  some  extent  a  review  of  the  preceding  observa- 
tions, was  written  with  the  view  of  emphasising  the  important  bearing 
thai  an  intimate  study  of  myocardial  changes  in  infective  diseases  has 
upon  the  clinical  study  of  organic  heart  disease.  Although  it  is  but 
an  insignificant  contribution  in  itself,  we  have  included  it  here  to 
illustrate  that  our  constant  endeavour  has  been  to  apply  the  results 
of  experimental  and  laboratory  observation  to  the  problems  of  practical 
medicine. 

This  subject  is  one  that  has  naturally  attracted  the  attention 
of  many  observers,  and  is  in  danger  of  being  considered  already 
too  well  worn.  It  seems,  however,  possible  that  a  systematic 
examination  of  the  myocardium  in  various  conditions  may 
prove  of  great  value  in  the  study  of  cardiac  diseases.  This 
is  the  more  probable  because  pathology  affords  a  continual 
assistance  both  by  the  improvements  in  its  methods  and  the 
new  light  that  bacteriology  throws  upon  even  well-established 
facts.  In  the  clinical  study  of  heart  disease  the  detection 
of  a  valvular  murmur  or  pericardial  friction  sound  is  among 
the  surest  evidences  of  organic  heart  disease,  and  the  endo- 
cardium and  pericardium  accordingly  take  a  most  prominent 
position  in  the  clinical  history.  To  the  morbid  anatomy 
of  the  heart  much  the  same  applies,  for  the  evidences  of 
endocarditis  or  pericarditis,  recent  or  of  old  standing,  are 
more  easily  recognised  than  are  similar  changes  in  the  cardiac 
wall  itself.  Possibly  then  it  may  be  that  over  much  has 
been  attributed  to  the  damage  of  these  structures,  with  the 
result  that  the  myocardium  has  been  regarded  rather  as  a 
passive  structure  than  an  active  muscular  wall,  and  that 
mechanical  explanations  have  taken  too  great  a  part  in  the 

63 


64    OBSERVATIONS  UPON  THE  PATHOLOGY 

interpretation  of  the  morbid  results  that  are  presented.  In 
view  of  this  possibility  it  is  a  suggestive  statement— the  outcome 
of  experience — that  in  judging  of  the  gravity  of  a  case  of 
organic  heart  disease  the  symptoms  are  of  more  import  than 
the  physical  signs,  for  the  symptoms  are  mostly  determined 
by  the  failure  of  the  circulation  due  to  the  enfeeblement  of 
the  heart-wall,  whereas  the  physical  signs  are  determined 
mostly  by  the  nature  and  extent  of  the  valvular  lesion.  It 
is  suggestive  also  that  in  chronic  heart  disease  of  rheumatic 
origin,  when  failure  of  compensation  occurs,  there  is  not  as 
a  rule  a  history  of  mechanical  overstrain,  but  frequently  in 
adults  and  almost  invariably  in  childhood,  a  history  of  a  relapse 
of  rheumatism. 

The  widest  field  for  investigations  upon  the  myocardium  is 
provided  by  rheumatic  fever,  because  of  its  frequent  occur- 
rence, and  because,  though  it  varies  much  in  its  severity,  it 
usually  gives  rise  to  considerable  resistance  within  the  body. 
This  resistance  is  apparent  in  the  inflammation,  fibrinous 
exudation,  and  fibrosis  that  result  from  its  invasion. 

Since  these  phenomena  of  inflammation  take  place  in  the 
neighbourhood  of  the  vessels,  and  must  be  to  some  extent 
modified  by  the  mechanical  surroundings,  the  arrangement  of 
the  coronary  circulation  within  the  heart  becomes  a  question 
of  some  interest.  If  a  section  is  made  transversely  across  the 
base  of  the  heart  through  the  valve  rings,  numerous  vessels 
can  be  seen  arranged  in  an  areolar  tissue  beneath  the  endo- 
cardium around  the  orifices.  A  vertical  section  through  the 
mitral  valve  and  auriculo-ventricular  junctions  of  a  heart  in- 
jected with  Prussian  blue,  shows  these  vessels  lying  in  the 
connective  tissue  at  the  base  of  the  valve,  and  in  the  valve 
itself  lacunae  are  also  visible.  A  similar  section  through  an 
inflamed  valve  shows  a  considerable  exudation  in  the  areolar 
tissue  at  the  base  of  the  valve  in  the  region  of  these  vessels. 
In  the  acute  and  severe  cases  of  rheumatic  fever  this  cellular 
exudation  can  be  traced  around  the  vessels  beneath  the  endo- 
cardium of  the  auricle  and  ventricle,  but  may  give  rise  to  no 
visible  sign  upon  the  surface  of  the  endocardium.  If,  how- 
ever, the  leucocytic  infiltration  invades  the  endocardium 
from  beneath,  as  it  may  invade  the  valve  from  its  base,  then 
yellow  points  can  be  detected  upon  the  surface.  The  peri- 
cardium  when   inflamed   shows   similar   changes   even   more 


OF  THE  MYOCARDIUM  65 

definitely,  for  there  is  a  free  surface  toward  the  pericardial 
cavity,  and  the  deep  part  of  the  visceral  layer  contains  numerous 
vessels.  Should  the  inflammation  be  subacute,  the  develop- 
ment of  fibroblasts  and  the  earlier  stages  of  formation  of  an 
adherent  pericardium  can  be  readily  traced.  A  study  of  the 
arrangement  of  the  vessels  around  the  mitral  orifice,  by  vertical 
and  transverse  sections  in  healthy  and  diseased  conditions, 
coupled  with  a  study  of  the  changes  in  an  inflamed  pericardium, 
gives  perhaps  the  most  realistic  picture  possible  of  the  develop- 
ment of  mitral  stenosis  as  an  after-result  of  rheumatism. 

In  the  wall  of  the  heart  the  capillaries  are  seen  to  run  between 
the  several  muscular  fibres,  and  are  encompassed  by  muscular 
walls.  In  the  intermuscular  septa  there  is  some  areolar  tissue, 
and  in  at  any  rate  some  cases  of  rheumatic  heart  disease 
cellular  exudation  can  be  traced  at  these  points  spreading 
through  the  heart  wall  in  scattered  foci.  These  foci  have  been 
found  in  a  case  where  pericarditis  was  only  manifested  the 
day  before  death,  and  also  in  cases  of  recurrent  rheumatism 
where  the  pericardium  was  adherent,  and  not  in  a  condition 
of  acute  inflammation.  In  some  cases  of  recurrent  rheu- 
matism, also,  there  is  an  increase  in  the  interstitial  tissues  of 
the  heart  wall  :  a  fibrosis  spreading  from  the  vessels,  and 
implicating  the  adjacent  muscular  bundles,  analogous  to  the 
fibrosis  of  the  valves  or  pericardium.  The  question  arises, 
whether  these  changes  in  the  heart  wall  itself,  are  secondary 
to  a  pericarditis,  coincident  or  even  independent  of  that  ? 
At  first  sight,  perhaps,  this  may  seem  a  point  of  small  im- 
portance,, but  from  the  clinical  aspect  it  is  a  question  of  great 
interest.  If  the  myocardial  inflammation  is  secondary  to 
pericarditis,  then  the  occurrence  of  pericarditis  is  doubly  grave 
by  reason  of  the  injury  to  the  pericardium  itself  and  to  the 
heart  wall  also.  But  if  the  myocardial  changes  may  arise 
independently,  then  it  is  possible  that  many  cases  of  acute 
rheumatism  in  which  there  is  no  pericarditis  may  cripple 
the  heart  in  this  insidious  way,  especially  if  the  pericardium 
is  already  adherent.  One  case  is  of  value  in  this  connection. 
The  patient,  a  young  woman,  died  in  the  third  attack  of  rheu- 
matism. There  was  mitral  valvulitis  and  great  dilatation, 
but  macroscopically  no  pericarditis.  Upon  microscopic  ex- 
amination there  was  evidence  of  myocarditis,  and  pericarditis 
was   just   commencing.     Other   observers   have    only   found 


66    OBSERVATIONS  UPON  THE  PATHOLOGY 

changes  in  the  superficial  layers  of  the  heart  wall  immediately 
beneath  the  inflamed  pericardium,  and  the  recent  researches  of 
Professor  Hill  and  Mr.  Barnard  have  increased  our  know- 
ledge of  the  function  of  the  pericardium  as  a  support  to  the 
heart  wall  ;  also,  too,  these  observations  have  been  utilised 
by  Dr.  Sequeira  in  a  paper  recently  read  before  the  Royal 
Medical  and  Chirurgical  Society  to  explain  the  grave  im- 
portance of  pericarditis  as  a  cause  of  cardiac  dilatation. 
Nevertheless,  there  is  much  in  favour  of  the  view  that  myo- 
cardial changes  are  not  necessarily  dependent  upon  peri- 
carditis ;  and  though  the  pericardium  may  have  an  important 
function  in  checking  dilatation,  that  dilatation,  and  marked 
dilatation,  too,  may  occur  without  any  weakening  of  the 
pericardium  by  pericarditis. 

The  condition  of  the  cardiac  muscle  in  rheumatic  fever  is 
the  next  point  that  claims  attention,  and  is  a  question  sur- 
rounded with  difficulties.  It  may  be  generally  asserted  that 
the  more  specialised  a  tissue  the  more  difficult  it  is  to  feel 
sure  of  the  existence  of  morbid  changes  in  its  structure,  and 
of  their  proper  interpretation.  This  is  a  difficulty,  too,  which 
is  enhanced  by  the  post-mortem  changes  that  occur  in  the 
tissues.  Nevertheless,  whatever  view  be  taken  of  the  actual 
cause  of  rheumatism,  it  is  generally  allowed  that  there  is  an 
alteration  in  the  blood  state,  and  this  raises  the  possibility  of 
the  cardiac  muscle  suffering  as  a  consequence.  Moreover, 
there  is  considerable  evidence  in  favour  of  this  view.  In  some 
rare  cases  of  rheumatism  death  has  occurred  from  cardiac 
failure  with  dilatation,  and  no  pericarditis  has  been  found 
after  death.  Recently  in  two  acute  cases  of  rheumatism  with 
pericarditis  general  fatty  changes  were  found  throughout  the 
heart,  including  the  papillary  muscles.  Though  this  is  not 
conclusive — for  it  may  be  possibly  objected  that  this  change  is 
not  a  primary  one,  but  secondary  to  the  enfeebled  circulation — 
nevertheless,  it  points,  strongly  to  some  profound  injury 
to  the  cardiac  muscle,  which  has  resulted  in  this  circulatory 
failure.  In  a  question  of  this  kind  the  complexity  of  the 
chemical  processes  within  the  body  requires  to  be  remembered, 
and  it  is  very  possible  that  the  particular  condition  which  is 
recognised  by  certain  comparatively  rough  staining  methods 
as  a  fatty  change  may  be  the  end  result  of  widely  different 
antecedent  chemical  processes.     There  are  other  alterations, 


OF  THE  MYOCARDIUM  67 

too,  in  the  cardiac  muscle  in  acute  rheumatism  beside  these 
fatty  changes,  such  as  hyaline  degeneration,  loss  of  striation, 
and  vacuolisation.  Even  in  children  granules  sometimes 
staining  with  thionin  can  be  detected  in  the  region  of  the 
nucleus,  and  the  nucleus  itself  may  also  show  numerous 
granules.  This  brief  allusion  to  the  alterations  in  the  cardiac 
muscle  is  made  rather  with  the  object  of  showing  that  caution 
is  required  before  pronouncing  that  the  muscle  is  not  affected 
in  rheumatism,  than  with  the  intention  of  stating  that  it  is 
invariably  affected.  Far  more  numerous  observations  are 
required  to  settle  such  a  point,  and  experimental  pathology 
must  be  requisitioned  before  the  true  value  can  be  attached 
to  these  more  obscure  morbid  changes  in  the  muscle.  The 
implication  of  the  cardiac  nerves  is  another  important  question. 

There  is  one  other  condition  somewhat  rare  in  its  occur- 
rence but  of  deep  clinical  interest  in  which  the  myocardium 
may  show  much  disease.  During  life  the  symptoms  are  those 
of  breathlessness,  angina,  and  a  tendency  to  syncope.  The  end 
is  usually  quite  sudden,  and  the  necropsy  shows  as  the  most 
striking  feature  an  acute  inflammation  of  the  aorta.  Two 
such  cases  we  examined  and  published  fully  in  the  Lancet  in 
May  1899  illustrated  this.  It  was  evident  that  in  these  cases 
analogous  changes  were  proceeding  in  the  heart  and  arterial 
wall. 

In  conclusion  an  endeavour  has  been  made  in  this  paper  to 
support  the  view  that  a  systematic  investigation  of  the  cardiac 
muscle  may  prove  of  some  practical  value  in  the  study  of  cardiac 
diseases,  especially  if  the  clinical  facts  can  be  at  the  same 
time  recorded. 


PAPER  NO.  V 

THREE  FATAL  CASES  OF  EXTENSIVE  VENOUS 

THROMBOSIS  ASSOCIATED  WITH  SEVERE 

RHEUMATIC  CARDITIS 

(Reprinted  from  the  Lancet,  July  23,  1898.) 

The  three  cases  recorded  here  arc,  we  believe,  of  sufficient  rarity  to  be 
of  interest  in  themselves.  The  pathological  investigations  bring  addi- 
tional support  to  the  contention  that  the  rheumatic  processes  within 
the  body  are  the  result  of  some  infective  process. 

The  first  case,  that  of  a  girl  aged  nineteen  years,  was 
admitted  into  St.  Mary's  Hospital,  under  the  care  of  Dr. 
D.  B.  Lees,  for  shortness  of  breath  and  swelling  of  the  arms  and 
legs.  In  January  1897,  she  had  suffered  from  a  very  severe 
attack  of  rheumatic  fever  for  which  she  had  been  kept  in  bed 
for  thirteen  weeks  and  during  this  time  she  was  reported  to 
have  had  both  pneumonia  and  peritonitis.  The  history  of 
this  present  illness  dated  from  August  1897,  when  the  patient 
noticed  swelling  of  the  legs  and  abdomen  ;  in  September, 
however,  there  was  decided  improvement.  In  the  first 
week  in  October  the  symptoms  again  became  more  urgent  and 
a  few  days  before  admission  to  hospital  the  left  arm  suddenly 
commenced  to  swell.  On  admission,  on  October  19,  her  con- 
dition was  extremely  grave.  She  was  very  pale  and  distressed. 
The  conjunctivae  were  icteric  and  there  was  orthopneea. 
The  temperature  was  subnormal  and  remained  so  throughout 
the  illness.  The  legs  and  thighs  were  cedematous.  The 
left  arm  and  hand  were  much  swollen  and  the  face  was  puffy  ; 
the  right  upper  extremity  pitted  on  pressure  and  the  upper 
part  of  the  chest  was  cedematous.  The  cardiac  condition 
was  that  of  advanced  organic  disease.  The  pulse  was  90  and 
very  irregular  in  force  and  frequencv.     Not  all  the  beats  of  the 

68 


EXTENSIVE  VENOUS  THROMBOSIS  69 

heart  were  perceptible  at  the  wrist.  The  impulse  was  diffuse 
and  the  heart  was  much  and  generally  dilated.  A  systolic 
apical  murmur  was  heard  and  an  accentuated  pulmonary 
second  sound.  The  air  entry  and  percussion  note  were  im- 
paired at  both  bases  posteriorly.  The  liver  was  large  and 
tender  and  the  urine  contained  some  albumin  and  was  loaded 
with  urates.  For  the  next  few  days  there  was  some  slight 
improvement,  but  at  midnight  on  October  31,  the  patient 
became  aphasic,  the  right  hand  appeared  to  be  weak,  and  the 
right  leg  was  kept  semi-flexed.  Deviation  of  the  head  and 
eyes  did  not  occur.  She  appeared  to  understand  what  was 
said,  but  gradually  became  more  and  more  drowsy.  Then 
followed  loss  of  sphincter  control,  difficulty  in  swallowing,  coma, 
and  finally  death. 

A  post-mortem  examination  was  made  twenty-four  hours 
after  death.  The  pericardium  was  found  totally  adherent, 
in  places  firmly  and  in  other  parts  only  feebly  so.  Both 
auricular  appendices  were  compressed  by  the  pericardium 
and  round  the  large  vessels  the  pericardial  and  mediastinal 
tissues  were  cedematous.  The  heart  weighed  16  oz.  and  the 
cavities  were  dilated,  especially  that  of  the  right  ventricle. 
The  mitral  orifice  was  slightly  narrowed  by  old  rheumatic 
endocarditis,  but  the  deformity  of  the  valve  was  moderate. 
The  aortic  valve  was  incompetent  from  previous  rheumatic 
endocarditis.  The  tricuspid  valve  was  incompetent  but  there 
were  no  rheumatic  changes  in  this  valve.  The  pulmonary 
valve  was  natural.  The  right  auricle  was  empty.  The  left 
ventricle  was  ij  in.  thick.  The  muscle  was  firm  and  of  good 
colour.  Both  lungs  were  adherent  to  the  chest  wall.  Both 
internal  jugular  veins  were  like  firm  cords  and  contained 
adherent  clot  throughout  their  entire  extent.  The  lower  end 
of  the  left  internal  jugular  was  white  and  narrowed  and  very 
firm.  Both  venae  innominatae  contained  adherent  clot  and 
the  left  one  could  hardly  be  recognised  amongst  the  cedematous 
tissue  of  the  mediastinum.  The  upper  part  of  the  superior 
vena  cava  contained  clot  which  was  firmly  adherent  to  one 
side  of  the  wall  of  the  vein  but  did  not  occlude  the  entire 
lumen  or  project  into  the  auricle.  There  was  no  clot  in  the 
inferior  vena  cava.  The  brain  was  generally  softened  but  no 
change  was  found  locally  or  in  any  particular  vessels.  The 
liver  showed  advanced  chronic  congestion  due  to  tricuspid 


jo  EXTENSIVE  VENOUS  THROMBOSIS 

incompetence.     The    kidneys    were    indurated   from    chronic 
venous  congestion. 

The  second  patient  a  young  woman,  aged  twenty-one 
years  was  admitted  to  the  hospital  under  the  care  of 
Dr.  Cheadle  on  February  9,  1898.  When  a  child  she  had 
suffered  from  an  attack  of  scarlet  fever  which  was  followed 
shortly  afterwards  by  an  attack  of  rheumatic  fever.  Two 
years  before  the  present  illness  she  suffered  from  a  second  attack 
of  rheumatic  fever.  The  final  illness  began  gradually  with 
weakness,  increasing  dyspnoea  and  oedema  of  the  face  and  legs. 
On  admission  to  hospital  the  patient  was  very  ill,  the  face 
was  puffy,  and  she  was  very  anaemic.  The  temperature  was 
ioi°  F.,  the  pulse  averaged  128  and  the  respirations  28.  The 
legs  pitted  on  pressure.  The  pulse  was  regular  and  of  low 
tension ;  the  heart  was  dilated.  On  auscultation  a  loud 
systolic  murmur  was  heard  all  over  the  front  and  back  of  the 
chest  ;  the  impulse  was  diffuse  and  a  systolic  thrill  could  be 
felt.  Bronchitic  sounds  were  heard  over  both  lungs.  Neither 
the  liver  nor  the  spleen  could  be  felt  below  the  costal  arch. 
The  urine  contained  albumin,  blood  and  some  tube  casts,  and 
the  specific  gravity  was  1020.  During  the  next  week  there  was 
marked  dilatation  of  the  heart,  with  irregular  pyrexia,  free 
sweating,  and  decided  increase  in  the  oedema  and  dyspnoea. 
On  February  18,  the  liver  and  spleen  could  both  be  felt  below 
the  costal  margin.  The  urine  was  scanty  and  contained 
albumin  and  blood,  but  no  more  casts  were  found  in  spite  of 
repeated  and  careful  search.  One  special  feature  of  this  case 
was  a  frequent  and  harassing  cough,  for  which  there  was  no 
apparent  explanation.  On  the  21st  there  was  complaint  of 
pain  in  the  wrists  and  left  forearm,  the  face  was  more  puffy 
and  the  conjunctivae  were  icteric  ;  the  pain  in  the  forearm 
was  localised  to  the  inner  side  over  the  region  of  the  flexor 
carpi  ulnaris  and  palmaris  longus  ;  this  area  was  very  tender, 
but  there  was  no  local  redness.  During  the  next  week  there 
was  distinct  improvement  and  the  heart  became  smaller,  but 
this  was  not  maintained  and  in  the  first  fortnight  of  March  the 
pyrexia,  which  had  been  persistent,  became  more  marked 
and  more  irregular.  The  pulse  was  now  irregular  and  there 
was  orthopncea,  with  attacks  of  severe  dyspnoea.  On  March 
17,  sudden  pain  was  felt  in  the  left  loin  and  more  blood  appeared 
in  the  urine.    The  left  lung  was  dull  at  the  base  and  over  a  con- 


IN  RHEUMATIC  CARDITIS  71 

siderable  area  tubular  breathing  was  heard.  The  face,  which 
had  become  almost  free  from  oedema,  now  again  became  puffy, 
especially  upon  the  left  side.  On  the  19th  some  casts  were 
again  found  in  the  urine  together  with  blood,  the  heart  was 
very  dilated,  and  the  patient  was  moribund.  She  died  on 
March  20. 

At  the  post-mortem  examination  which  was  made  on  March 
21,  the  pericardium  contained  a  slight  excess  of  clear  fluid, 
but  there  was  no   definite  pericarditis.     The  heart  weighed 
14  oz.     All  the  cavities  were  much  dilated  ;   in  addition  there 
was  distinct  hypertrophy  of  both  ventricles  and  of  the  left, 
auricle.     The  muscle  was  pale.     The  mitral  orifice  was  slightly 
larger  than  natural,  as  also  was  the  tricuspid.     There  were 
numerous  exuberant   granulations   on  the  mitral   valve  and 
a  portion  of  the  anterior  cusp  was  free,  the  chordae  tendineae 
attaching  it  to  the  papillary  muscle    having  ulcerated  and 
given  way.     Vegetations  had  also  spread  along  the  anterior 
wall  of  the  left  auricle  upon  the  inner  surface.     On  the  wall 
of  the  left  ventricle  below  the  mitral  valve  were  a  few  isolated 
vegetations.     The    tricuspid,    aortic,    and    pulmonary    valves 
were  not  affected.     The  lower  lobe  of  the  left  lung  was  solid 
with  pneumonic  change  ;    the  right  lower  lobe  was  extremely 
congested  but  did  not  sink  in  water.     The  spleen  weighed  8  oz. 
and  there  were  two  infarcts  within  it,  one  of  which  was  quite 
recent.     The    liver    weighed    44    oz.    and    was    fatty.     Each 
kidney  weighed  6  oz.  and  contained  one  infarct  ;    the  capsule 
of  each  was  thickened  but  not  adherent  ;   the  cortex  was  pale. 
In  the  left  internal  jugular  vein  was  a  clot  extending  from 
the  junction  with  the  left  subclavian  to  the  angle  of  the  jaw. 
This  was  pale  and  adherent  to  the  wall,  especially  in  the  lower 
part,  where  the  vein  was  cord-like.     The  innominate  veins 
and  right  jugular,  and  the  inferior  vena  cava  and  its  larger 
tributaries  were  not  affected.     The  brain  appeared  to  be  quite 
natural. 

The  microscopical  examination  was  undertaken  with  the 
assistance  of  Mr.  Brincker.  The  pericardium  showed  in 
the  visceral  layer  some  early  inflammation.  The  heart 
muscle  had  lost  much  of  its  striation  and  most  of  the 
fibres  showed  pigmented  perinuclear  granules.  The  mitral 
valve  was  much  affected  by  inflammation,  but  no  micro- 
organisms were  demonstrated  in  the  granulations.     Sections 


72  EXTENSIVE  VENOUS  THROMBOSIS 

of  the  left  internal  jugular  vein  showed  an  organising  thrombus, 
but  micro-organisms  could  not  be  demonstrated  in  the  vein 
wall,  which  was  not  distinctly  thickened.  No  organisms  were 
found  in  the  clot.  Sections  of  the  right  internal  jugular, 
appeared  to  be  natural.  The  left  lung  was  pneumonic  and 
numerous  diplococci  were  demonstrated  by  Gram's  method. 
The  kidneys  showed  no  sign  of  interstitial  inflammation 
from  any  old-standing  nephritis.  In  the  neighbourhood  of 
the  infarcts  there  were  haemorrhages  in  the  substance,  and 
the  renal  epithelium  showed  much  cloudy  swelling,  but 
otherwise  nothing  remarkable  was  observed. 

A  third  case,  that  of  a  girl  aged  nine  years,  was  admitted 
to  the  hospital  under  the  care  of  Dr.  Cheadle  on  February  19, 
1898,  for  swelling  of  the  body  and  limbs  and  collapse.  Two 
years  previously  she  had  suffered  from  an  attack  of  scarlet 
fever,  since  which  time  the  heart  had  been  affected.  There 
was  a  marked  rheumatic  history  upon  the  father's  side.  The 
mother  unfortunately  was  addicted  to  alcoholism,  so  that  it 
was  not  possible  to  obtain  a  careful  description  of  the  onset 
of  the  present  illness.  The  child  had  been  ailing  for  three 
weeks  with  pain  in  the  chest  and  cough,  and  during  the  last 
week  dropsy  was  noticed.  On  admission  to  hospital  the 
patient  was  very  pale  and  the  face  was  cedematous,  the  ex- 
pression being  distressed.  There  were  slight  cyanosis  and 
orthopneea.  The  temperature  was  97. 40  F.,  the  pulse  averaged 
100,  and  the  respirations  30.  The  fingers  were  clubbed,  the 
lower  extremities  were  cedematous,  and  the  front  of  the 
chest  pitted  on  pressure.  The  abdomen  contained  some 
fluid.  The  pulse  was  irregular,  weak  and  small.  The  heart 
was  much  enlarged  ;  the  left  limit  was  four  finger-breadths 
external  to  the  left  nipple  and  the  right  limit  was  three  finger- 
breadths  external  to  the  right  margin  of  the  sternum.  There 
were  marked  epigastric  pulsation,  praecordial  bulging,  and  a 
systolic  and  diastolic  thrill.  At  the  apex  a  systolic  murmur 
was  heard  and  over  the  aortic  cartilage  systolic  and  diastolic 
murmurs  were  audible.  There  was  also  a  doubtful  pericardial 
scratching  sound  heard  to  the  left  of  the  sternum.  The  air 
entry  was  impaired  over  the  bases  of  both  lungs  and  there 
were  scattered  rhonchi  and  sibili  over  both  the  front  and  the 
back  of  the  chest.  The  appetite  was  good,  though  the  tongue 
was  furred.     The  urine  was  acid,  the  specific  gravity  being 


IN  RHEUMATIC  CARDITIS  73 

1025  ;    it  contained  albumin  and  blood,  but  no  casts.     The 
liver  was  enlarged  and  pulsating.     The  child  slept  with  her 
face  turned  towards  the  pillow.     After  admission  to  hospital 
the  oedema  gradually  subsided  and  the  blood  in  the  urine 
disappeared.     Steady    improvement    was    maintained    until 
March  10,  when  pleural  friction  was  heard  in  the  left  axilla 
and  there  was  distinct  dullness  on  percussion  at  the  left  base. 
The  urine  contained  a  trace  of  blood,  but  there  was  not  any  rise 
of  temperature.     After  this  outbreak  there  was  again  improve- 
ment, the  oedema  disappeared,  the  liver  became  smaller,  and 
the  signs  in  the  left  pleural  cavity  cleared  up.     On  April  10, 
there  was  once  more  pain  in  the  left  side  and  also  dullness  at 
both  bases.     The  axillary  glands  were  noticed  to  be  enlarged. 
The  heart  was  more  dilated  and  the  action  was  feebler  ;    the 
liver  also  had  increased  in  size.     On  the  13th  the  left  side  of 
the  face  became  swollen  and  on  the  16th  there  was  marked 
oedema  of  the  right  side  of  the  neck,  the  face  was  purple,  and 
the  eyelids  and  lips  were  swollen.     Both  sides  of  the  neck 
were  tense,  and  tender  on  the  least  pressure.     Movement  of  the 
neck  was  painful.     The  temperature  was  subnormal ;    there 
was  no  swelling  of  the  legs  or  ascites.     Dr.  Cheadle  saw  the 
child  and  diagnosed  thrombosis  of  the  internal  jugular  veins. 
On  the  17th  the  right  arm  began  to  swell.     Shortly  after  the 
right  arm  had  become  swollen  the  left  arm  began  to  swell. 
The  chest  was   cedematous.     The  child  was  very  apathetic 
and  took  food  badly.     On  the  18th  she  was  very  drowsy  and 
apathetic  and  the  face  was  cyanosed.     At  midday  there  was 
sudden  dyspnoea  and  two  attacks  of  great  restlessness  occurred. 
The  extremities  became  cold  and  the  pulse  at  the  wrist  was 
imperceptible  ;    there  was  much  suffering.     On  the  19th  the 
oedema  of  the  right  arm  was  extreme  and  there  was  tenderness 
on  pressure,  but  the  face  was  less  swollen.     The  respiration 
was  slow  and  sighing.     On  the  20th  two  firm  cords  were  felt  in 
the  lower  part  of  the  neck.     The  legs  and  feet  were  a  little 
swollen.     The  area  of  cardiac  dullness  was  now  enormous  and 
there  was  loud  general  pericardial  friction.     Sharp  crepita- 
tions were  heard  over  both  lungs.     The  urine  was  scanty  ;   it 
contained  a  trace  of  albumin  and  no  blood.     Food  was  refused 
and  death  took  place  on  the  21st. 

A  post-mortem   examination  was  made   on   February   22. 
The  cranial  cavity  was  not  opened.     The  pericardium  contained 


74  EXTENSIVE  VENOUS  THROMBOSIS 

between  4  oz.  and  5  oz.  of  turbid  fluid  and  the  surfaces  were 
coated  with  recent    lymph.      All  the  cavities  of    the  heart 
were  dilated.     Both  ventricles  were  hypertrophied,  the  right 
proportionately  more  than  the  left.     The  mitral  orifice  was 
incompetent,  the  valve  segments  and  chordae  tendineae  were 
thickened,    and    in    addition    along    the    cusps    were    some 
recent   vegetations.     The    tricuspid  orifice   was    incompetent 
and  along  the  cusps  were  recent  vegetations.     The  auricles 
were  dilated,  but  the  right  auricle  was  empty.     The  aortic 
valves   were    thickened   and   incompetent    and   beaded   with 
recent    vegetations.     The    pulmonary    valves    were    natural. 
The  following  veins  were  occluded  by  thrombus  :    the  right 
innominate,    subclavian,     axillary,     internal     and     external 
jugulars — the  last  only  in  the  lower  part  of  its  course  ;  the  left 
internal  jugular,  external  jugular,  inferior  thyroid,  axillary, 
subclavian    and    innominate.     In    its    upper    two-thirds    the 
superior  vena  cava  was  occluded.     Looking  into  it  from  the 
auricle  a  pale,  soft  clot  could  be  seen,  not  adherent,  blocking 
completely  the  lumen  of  the  vessel  ;    higher  up  the  clot  was 
quite  firm.   Both  internal  jugulars  felt  like  firm  cords  in  their 
lower  part  and  were  white  and  small,  whereas  in  the  upper  part 
they  were  bulged  with  soft  clot.     The  left  innominate  was  small 
and  white  and  only  admitted  a  small  probe.     The  veins  were 
more  adherent  to  the  surrounding  tissues  than  usual.     Though 
more  extensive  it  is  quite  comparable  to  the  condition  found  in 
Case  1,  but  there  was  no  pericardial  adhesion  or  obliteration 
of  auricular  appendices  as  in  the  latter.     The  inferior  vena 
cava  and  its  tributaries  were  natural.     Unfortunately,  whether 
as  in  the  first  case  the  brain  was  oedematous  or  whether  the 
lateral  sinuses  were  occluded  could  not  be  ascertained.     It  is, 
however,   certain   that   the   clotting   did   not    begin   in   these 
sinuses,  for  the  further  the  distance  from  them  the  older  was 
the  thrombosis  in  the  jugular  veins.     Nodules  were  present 
on  the  dorsum  of  the  right  foot  and  in  the  scalp.     The  re- 
maining organs   showed  the   usual   secondary  changes   from 
advanced   morbus    cordis.       There    was    no    evidence   of    in- 
farction. 

Cultivations  from  the  pericardial  fluid,  lymph,  and  blood- 
clot  were  negative,  as  also  were  films  made  from  the  pericardial 
fluid  and  blood-clot.  The  conditions  of  the  heart  wall  and 
pericardium    are    of    interest    because    they    represented    the 


FIG.  10 
Illustration  representing  the  thrombosis  of  the  veins  in  Case  3. 

A.  Soft  clot  in  the  left  distended  internal  jugular  vein. 

B.  The  same  vein  containing  firm  clot. 

C.  Left  subclavian  vein. 

D.  Left  innominate  vein. 

E.  Inferior  thyroid  vein. 

F.  Eight  innominate  vein. 

G.  Superior  vena  cava. 
H.  Eight  subclavian  vein. 

I.   Eight  internal  jugular  vein. 

The  external  jugular  veins  are  not  shown. 


IN  RHEUMATIC  CARDITIS  75 

condition  of  a  very  acute  rheumatic  carditis.  As  regards  the 
pericardium  the  vessels  in  the  subserous  areolar  tissue  of  the 
visceral  layer  were  extremely  congested  and  the  areolar  tissue 
surrounding  them  was  much  swollen  and  hyaline  in  appearance. 
The  superficial  connective  tissue  layer  contained  numerous 
inflammatory  cells,  and,  finally,  there  was  an  adherent  layer 
of  lymph,  the  serous  epithelium  having  disappeared.  The 
same  process  could  be  traced  throughout  the  heart  wall  along 
the  course  of  the  vessels  ;  there  was  the  same  swelling  of  the 
connective  tissue  supporting  them  and  the  same  inflammatory 
cell  exudation  which  could  be  traced  even  between  the  muscle 
fasciculi  and  the  capillaries  between  the  fibres  were  dilated. 
Immediately  beneath  the  pericardium  the  process  was  quite 
distinct  and  there  was  loss  of  striation  but  no  gross  change 
was  apparent  in  these  superficial  layers  as  compared  with 
the  deeper.  The  muscle  fibres,  with  their  nutrition  altered 
thus  and  supplied  by  blood  probably  toxic  with  the  rheumatic 
poison,  must  necessarily  have  suffered  throughout  the  heart 
wall.  Sections  taken  through  a  papillary  muscle,  with  its 
chordae  and  a  part  of  the  mitral  valve,  showed  very  markedly 
this  interstitial  inflammation.  The  soft  clot  in  the  superior 
vena  cava  was  hardened  and  sections  were  cut,  but  no  organisms 
were  discovered.  A  series  of  sections  were  made  from  the 
right  brachial  vein  to  the  axillary7,  from  a  region  not  affected 
to  a  region  definitely  so.  Sections  of  the  vein  showed  the 
clot  gradually  permeated  by  spindle  and  round  cells,  with 
formation  of  a  network,  the  adhesion  of  the  clot  to  the  wall  of 
the  vein  first  at  one  place,  then  at  several,  by  means  of  branches 
spreading  in  from  the  intima,  and  finally  the  formation  of 
canals  lined  with  spindle  cells.  In  these  sections  the  vein 
wall  was  not  noticeably  thickened,  but  as  the  thrombus 
became  more  firmly  attached  there  was  evidence  of  early 
phlebo-sclerosis.  Doubtless  the  lowest  portion  of  the  internal 
jugulars  would  have  shown  this  process  more  definitely.  No 
micro-organisms  were  found  either  in  the  clot  or  in  the  vein 
itself.  A  section  from  the  left  brachial  showed  a  small  adherent 
thrombus  at  one  point,  slightly  diminishing  the  lumen  of  the 
vessel. 

Owing  to  the  detail  in  the  description  of  the  cases  given 
above  it  may  be  well  to  review  them  briefly  as  they  are  un- 
questionably of  different  value.     The  first  case  is  incomplete — ■ 


;6  EXTENSIVE  VENOUS  THROMBOSIS 

clinically  because  the  patient  was  such  a  short  time  under 
observation  and  pathologically  because,  ignorant  of  the  rarity 
of  the  condition,  no  minute  observations  were  made.  The 
second  case  is  an  unusual  one,  resembling  very  closely  malignant 
endocarditis.  It  is  included  with  the  other  two  because  no 
micro-organisms  were  found  upon  the  valves  and  more  es- 
pecially because,  the  aetiology  of  acute  rheumatism  being  still 
obscure,  the  exact  place  which  malignant  endocarditis  must 
take  in  relation  to  it  must  still  be  uncertain.  Having  pointed 
out  the  gradual  onset,  the  continued  pyrexia,  the  sweating, 
infarction,  and  ulceration  of  the  chordae  tendineae,  it  is  an  open 
question  as  to  whether  or  not  the  condition  is  comparable 
to  that  of  the  other  two  cases.  The  third  case  is  by  far  the 
most  complete,  for  the  diagnosis  was  made  some  days  before 
death  and  the  symptoms  were  accordingly  studied  with  more 
precision.  The  remarkable  similarity  in  the  distribution  of 
the  thrombosis  in  the  first  and  third  Cases  has  been  alluded 
to  earlier  in  this  article. 

In  a  comprehensive  paper  by  Gatay  on  La  Phlcbite  Rhcu- 
matismale *  two  views  are  put  forward  in  explanation  of 
rheumatic  thrombosis.  One  is  that  of  Schmidt,  who  con- 
sidered the  thrombosis  primary,  and  the  other  is  that  of 
Letulle  and  Gatay,  who  considered  a  rheumatic  phlebitis  to 
be  the  first  event.  Confining  attention  to  the  cases  mentioned 
above,  it  seems  to  us  impossible,  so  long  as  the  exact  aetiology 
of  rheumatic  fever  is  obscure,  to  decide  which  process  was 
the  initial  one.  It  is  certain  that  the  blood-current  was 
feeble,  for  the  heart  muscle  was  distinctly  affected  in  two  cases 
and  in  all  there  was  much  organic  disease  with  tricuspid  in- 
competence ;  the  blood  was  altered,  for  there  was  profound 
anaemia,  and  both  these  conditions  predispose  to  thrombosis. 
On  the  other  hand,  the  veins  most  affected  were  those  in  which 
the  circulation  was  aided  by  gravity,  especially  as  there  was 
orthopncea.  The  thrombosis  however  was  most  advanced 
where  the  vertical  current  in  the  jugular  stream  met  the  more 
or  less  cross  current  in  the  subclavians.  Again,  in  two  cases 
there  was  active  carditis,  which  suggests  the  possibility  of 
phlebitis,  and  in  one  case  there  was  periphlebitis.  Neverthe- 
less apart  from  the  periphlebitis  the  changes  found  were  not 
in  favour  of  a  primary  phlebitis.  So  much,  in  fact,  depends 
upon  the  exact  nature  of  the  rheumatic  process  that  in  such 


IN  RHEUMATIC  CARDITIS  77 

complicated  cases  as  these  are  it  seems  hazardous  to 
dogmatise. 

The  duration  of  the  thrombosis  is  a  point  which  has  con- 
siderable practical  interest.  The  changes  in  the  axillary 
vein  described  above  pointed  to  a  duration  of  at  least  eight 
days  and  the  condition  in  the  jugulars  was  of  considerably 
longer  standing.  Now  in  both  the  cases  under  observation  for 
some  weeks  there  was  varying  oedema  of  the  face,  noted  from 
the  time  of  admission,  an  occurrence  which  is  not  common  in 
cardiac  disease.  Again,  sections  of  one  vein  showed  in  some 
places  clot  adherent  in  one  place  only,  whilst  elsewhere  the 
lumen  was  free.  These  facts  point  to  the  possibility  of  a  gradual 
thrombosis  having  occurred  during  a  period  of  weeks,  with 
exacerbations  when  the  disease  flared  up,  producing  finally 
arrest  of  the  circulation.  It  is  possible  that  oedema  of  the  face, 
which  is  more  commonly  observed  in  the  advanced  morbus 
cordis  of  children,  may  in  some  cases,  depend  upon  the  occur- 
rence of  a  partial  thrombosis  of  this  kind. 

The  diagnosis  offers  some  difficulty.  In  the  third  case,  Dr. 
Cheadle  pointed  out  the  close  resemblance  in  the  appearance 
of  the  neck  to  severe  parotitis  or  to  angina  from  severe  throat 
affections.  Again,  when  there  are  blood  and  albumin  in  the 
urine  the  oedema  and  pallor  of  the  face  are  very  suggestive 
of  Bright 's  disease.  The  distinctive  features  are  the  local 
appearance  and  spread  of  the  oedema,  the  marked  tenderness, 
and  the  extreme  swelling  and  in  the  severe  cases,  pain  on 
moving  the  head.  The  feeling  of  the  firm  cords  in  the  neck 
is  convincing,  but  not  an  easy  observation  because  of  the 
danger  of  any  but  the  lightest  manipulation,  and  also  the 
tenderness  and  the  rigidity  of  the  inner  heads  of  the  sterno- 
mastoids.  Mental  apathy  is  a  remarkable  symptom.  The 
prognosis  of  these  cases,  apart  from  the  thromboses,  is  ex- 
ceedingly grave,  and  that  they  introduce  an  additional  element 
is  shown  by  the  occurrence  of  aphasia  and  a  gradual  coma 
in  the  first  case  and  sudden  dyspnoea  and  pulselessness  in  the 
second.  The  treatment  must  necessarily  be  considered  from 
the  vieW  of  the  general  condition  present,  and  great  care  in 
moving  the  patient  is  necessary  where  there  is  this  additional 
complication. 

Thrombosis  in  rheumatism  is  one  of  the  rarer  features  of  this 
disease.     Dr.  Archibald  Garrod  in  his  treatise  on  Rheumatism 


EXTENSIVE  VENOUS  THROMBOSIS 

makes  a  very  definite  allusion  to  it  and  quotes  the  researches 
of  Schmidt  and  Letulle  upon  the  condition.  Dr.  Cheadle 
mentioned  other  cases  he  had  met  with.  Gat  ay  in  his  paper 
in  1896  describes  two  cases  with  necropsies  ;  one  (Macaigne 
and  Lauren's  case)  showed  small-celled  infiltration  of  each 
coat  of  the  vein  and  desquamation  of  the  endothelium  followed 
by  an  inflammatory  change  in  thfc  vessel  wall.  Bacteriological 
results  were  negative.  In  this  case  thrombi  were  found 
in  the  brachial,  axillary,  and  subclavian  veins.  Renouard 
noted  difficulty  in  turning  the  neck  in  one  case.  Gatay  states 
that  it  can  attack  the  veins  of  the  neck,  but  it  is  exceptional 
for  it  to  start  in  the  jugulars.  One  case  is  quoted  where  a 
thrombus  was  found  in  the  external  jugular  only.  Macaigne 
and  Laurens  noted  in  their  case  the  heavy  mental  state. 
Petechia?,  erythemata,  and  fever  are  pointed  out  as  occurring 
simultaneously  with  the  thrombosis  and  the  veins  may  be 
arborescent  in  the  neighbourhood.  It  would  appear  from 
the  literature  on  the  subject  that  the  veins  of  the  extremities 
especially  of  the  lower  are  most  frequently  affected.  Two 
of  the  cases  recorded  above  certainly  appear  to  be  quite 
remarkable  both  in  their  similarity  and  the  great  extent  of 
the  thrombosis. 

1  La  Gazette  Hebdomadaire  de  Medecine  et  de  Chirnrgie,   February 
1896. 


PAPER  NO.  VI 

THE   HISTOLOGY   OF   THE   RHEUMATIC 
NODULE 

By  F.  J.  POYNTON,  M.D.,  and  G.  F.  STILL,  M.D. 

(Transactions  of  the  Pathological  Society  of  London; 
1899-) 

The  chief  interest  of  this  paper,  written  with  Dr.  G.  F.  Still,  lies  in 
the  demonstration  of  the  fact  that  the  structure  of  the  rheumatic  nodule 
is  essentially  compatible  with  that  of  a  lesion  produced  by  an  infective 
agent.  Insignificant  though  this  manifestation  of  rheumatism  may 
appear,  it  is  well  recognised  as  a  very  characteristic  result  of  an  acute 
rheumatic  process,  and  had  this  investigation  discovered  the  structure 
to  be  unlike  those  of  the  other  manifestations,  it  would  have  given  rise 
to  considerable  difficulties  in  explanation.  It  is  an  illuminating  fact, 
however,  that,  associated  as  the  nodule  usually  is  with  severe  rheumatic 
heart  disease,  the  structure  should  be  strictly  comparable  to  the  focal 
lesions  in  the  myocardium  ;  and  also  in  the  pericardium,  and  other 
serous  membranes,  in  severe  rheumatism.  Another  interesting  point 
is  the  bearing  that  nodules  of  this  kind  may  have  upon  the  explanation 
of  the  deeper  focal  lesions  in  the  muscles  that  occur  in  some  cases  0 
muscular  rheumatism. 

In  bringing  before  this  society  a  paper  upon  the  histology  of 
the  rheumatic  nodule,  we  are  fully  conscious  that  its  structure 
has  been  already  described  in  detail  by  many  excellent  ob- 
servers ;  but  we  venture  to  think  that  the  descriptions  which 
have  been  given,  especially  in  the  text -books  of  medicine, 
are  based  upon  appearances  that  are  found  when  the  nodule 
has  already  passed  through  the  earliest  stages  of  its  formation, 
and  for  that  reason  undue  stress  has  been  laid  upon  the  fibrous 
elements  which  are  then  so  evident.  The  essential  character 
of  the  nodule  is  to  be  judged  from  its  earliest  appearances, 
before  the  morbid  effects  of  the  rheumatic  poison  have  been 
modified  to  any  considerable  extent  by  the  reactive  processes 

79 


So  THE  HISTOLOGY  OF  THE 

that  occur  within  the  body  ;  and  it  is  from  a  study  of  these 
earlier  phenomena  that  one  sees  most  clearly  the  closeness 
of  the  analogy,  perhaps  the  actual  identity,  which  exists 
between  the  rheumatic  process,  as  seen  in  endocarditis  and 
pericarditis  with  that  seen  in  the  nodule,  a  relation  pointed  out 
long  ago  by  Dr.  Barlow  and  Dr.  Warner. 

It  is,  then,  to  the  earlier  phenomena  that  we  desire  to  call 
attention,  and  the  sections  shown  have  been  selected  as 
illustrating  this  stage  of  nodule  formation,  and  of  the  allied 
processes  in  the  endocardium  and  pericardium. 

We  may  perhaps  first  be  allowed  to  make  a  few  general 
observations  upon  the  difficulties  that  are  met  with  in  pre- 
paring sections  of  the  rheumatic  nodule,  and  to  call  attention 
to  certain  staining  processes  which  are  of  value  in  such  an  in- 
vestigation. In  the  first  place,  as  already  pointed  out,  it  is 
necessary  to  take  the  newer  formations,  and  not  those  of  many 
weeks'  standing,  and  to  ensure  this  it  will  probably  be  necessary 
to  take  the  smallest  that  can  be  obtained.  Further,  the 
section  must  pass  through  or  at  least  near  the  centre  of  the 
nodule,  for,  as  has  been  repeatedly  demonstrated,  the  micro- 
scopic appearances  at  the  periphery  are  very  different  from 
those  at  the  centre.  It  is  probable  that  the  difficulty  in 
carrying  out  these  precautions  account  in  some  degree  for  the 
discrepancies  in  the  descriptions  which  have  been  published. 
Finally,  certain  colour  reactions  given  by  the  aniline  dyes 
carbol-thionin  and  carbol-gentian  violet  give  considerable 
assistance  in  the  study  of  the  early  formation  of  the  nodule. 

The  value  of  thionin  as  a  nuclear  stain  was  first  pointed 
out  by  Martin  Heidenhain  in  the  "  Festschrift  fur  den  fiinfzigen 
Jahren  Jubillaume  Herrn  Dr.  Kolliker."  1  If  this  stain  be 
used  for  recent  fibrinous  exudations,  such  as  occur  in  rheumatic 
pericarditis,  or  in  pleurisy,  it  is  found  that  the  exudate  stains 
a  pale-blue  colour,  in  contrast  to  the  violet  blue  of  the  nuclei 
of  the  cellular  elements  and  fibrous  tissues.  If  this  exudation 
be  stained  by  Weigert's  fibrin  method  it  will  be  also  seen  that 
the  carbol-gentian  violet  gives  the  usual  reaction  for  that 
material. 

So  far  as  the  naked-eye  appearance  goes,  the  smallest  nodules 
which  can  be  appreciated  either  by  sight  or  touch  during  life 
are  by  no  means  the  smallest  which  can  be  seen  after  death. 
It  was  noted  on  several  occasions  that  where  only  a  few  nodules 


RHEUMATIC  NODULE  81 

could  be  found  on  the  head  during  life,  numerous  minute- 
deposits  of  the  same  yellowish-pink  material  were  visible  at  the 
post-mortem.  Some  of  these  deposits  were  more  or  less  rounded 
in  outline,  others  ran  together  into  irregular  areas,  each  with 
its  leash  of  small  dilated  blood-vessels  running  up  to  it,  the 
whole  being  too  small  to  be  appreciated  during  life.  The 
colour  of  these  minute  deposits  is  much  less  like  that  of  fibrous 
tissue  than  that  seen  in  the  older  nodules,  which  are  greyish 
white  rather  than  yellowish  pink.  On  attempting  to  remove 
one  of  these  smaller  nodules  there  is  considerable  difficulty, 
for  they  contain  a  certain  amount  of  fluid,  exudative  in  char- 
acter, and  any  squeezing  or  traction  diminishes  their  bulk, 
so  that  they  are  often  lost  altogether.  This  difficulty  is 
the  greater  because  there  is  no  distinct  line  of  demarcation 
from  the  surrounding  fibrous  tissue. 

Turning  now  to  the  microscopic  details,  we  should  like  to 
point  out  the  close  resemblance  that  there  is  between  the 
appearances  of  an  early  rheumatic  nodule  and  recent  rheumatic 
peri-  and  endo-carditis  when  stained  by  a  precisely  similar 
method. 

The  sections  shown  were  taken  from  a  case  that  died  in  St. 
Mary's  Hospital.  Three  weeks  elapsed  between  the  first 
visible  evidence  of  the  nodule  and  the  death  of  the  patient, 
and  thus,  though  not  in  its  very  earliest  condition,  it  still  shows 
distinctly  the  nature  of  the  early  changes. 

All  the  sections  were  from  tissues  fixed  in  corrosive  sublimate, 
they  were  cut  in  paraffin,  and  stained  with  carbol-thionin. 

In  the  centre  of  the  nodule  there  is  a  homogeneous  material 
arranged  in  layers  and  free  from  cellular  elements.  This 
stains  pale  blue  with  carbol-thionin  and  gives  Weigert's  fibrin 
reaction  with  gentian-violet.  We  look  upon  this  material  as 
fibrin  in  the  interstices  of  which  there  was  originally  fluid. 
It  is  the  presence  of  this  homogeneous  material  which  we  wish 
particularly  to  emphasise  :  for,  as  we  have  pointed  out  below, 
it  is  this,  and  not  the  subsequently  developed  fibrous  tissue, 
which  is,  in  our  opinion,  to  be  regarded  as  the  essential  element 
in  the  nodule.1  Compare  now  with  this  the  exudation  on  the 
free  surface  of  the  inflamed  pericardium,  and  the  vegetations 
on  the  valve,  and  it  will  be  seen  that  they  have  much  the  same 
appearance  and  give  the  same  reaction. 

Away  from  the  centre  of  the  nodule  towards  the  periphery, 

6 


82  THE  HISTOLOGY  OF  THE 

many  cellular  elements  become  visible  encroaching  upon  this 
fibrinous  centre  ;  and  again  comparison  with  the  deeper 
part  of  the  pericardial  exudation  and  with  the  valve  shows 
a  similar  appearance.  Still  further  towards  the  periphery  of 
the  nodule  fibrous  tissue  is  apparent,  some  of  it  swollen  and 
hyaline,  and  in  places  there  are  distended  and  tortuous  vessels. 
In  the  deeper  part  of  the  pericardium  also  the  distended 
vessels  are  very  apparent,  and  the  hyaline  appearance  of  its 
fibrous  matrix  is  also  distinct.  In  the  valve  the  swollen  appear- 
ance of  the  fibrous  tissue  can  also  be  detected. 

Thus  we  can  recognise  in  these  three  sections  fibrinous  exuda- 
tion, cellular  infiltration,  and  fibrous  tissue,  and  we  know  that 
in  the  pericardium  the  sequence  of  changes  is  as  follows  :  first, 
vascular  dilatation  ;  then  exudation,  which  in  rheumatism  is 
usually  fibrinous  ;  cellular  infiiltration  ;  and,  finally,  fibrosis. 
We  conclude  that  the  same  sequence  of  events  occurs  in  the 
rheumatic  nodule. 

In  this  way,  and  in  this  way  only,  it  seems  to  us  that  the 
occasional  rapid  appearance  and  disappearance  of  a  nodule 
can  be  explained,  for  if  the  rheumatic  process  is  rapid  and 
evanescent,  the  fibrinous  exudate  is  as  rapidly  absorbed,  and 
the  nodule,  which  in  such  a  case  is  probably  not  fibrous  at  all 
vanishes.  If  the  morbid  process  be  more  protracted,  then 
the  restorative  changes  will  be  slower,  and  there  will  be  some 
fibrosis  in  addition  to  absorption,  and  the  nodule  will  more 
slowly  disappear.  It  is  of  such  a  nodule  as  this  that  sections 
can  be  most  easily  obtained.  Now  and  again  the  nodule  lasts 
for  many  months,  and  the  section  of  such  a  one  shows  im- 
perfect restorative  processes,  the  fibrous  tissue  is  ill-formed 
and  only  to  be  found  in  patches,  a  condition  which  can  also 
be  observed  in  some  of  the  old  nodules  upon  the  cardiac  valves. 

We  are  aware  that  it  has  been  suggested  that  the  structure- 
less material  is  a  product  of  degeneration  in  the  nodule,  but 
this  suggestion  can  hardly,  we  think,  be  correct,  in  view  of 
the  fact  that  the  appearance  is  particularly  well  seen  in  the 
smaller  and  more  vascular  nodules  which  are  presumably  the 
young  ones,  and  therefore  the  least  likely  to  degenerate. 

A  study  of  nodules  in  various  stages  of  development  has 
seemed  to  us  to  show  that  this  central  portion,  consisting 
apparently  of  fibrinous  exudate,  is  the  basis,  so  to  speak,  of 
the  nodule,  and  it  is  from  this,  therefore,  and  not  from  the 


FIG.  11 

A  dissection  of  the  elbow-joint  of  a  child,  showing'  two  subcutaneous  nodules 

A.  Nodule  over  the  olecranon  process. 

B.  Nodule  over  the  outer  condyle. 

( From  the  museum  of  University  College  Hospital.) 


-,  *"\'-}  -;■•■.'  '-'J  ^Vi"3) 


FIG.  12 

Section  of  a  rheumatic  nodule  of  three  weeks  duration 

A.  Area  of  flbrino-cellular  exudation  and  necrosis. 

B.  Area  of  lencocytic  infiltration. 

C.  Area  of  swollen  fibrous  tissue. 


RHEUMATIC  NODULE  83 

peripheral  portion,  that  its  essential  character  must  be  judged. 
Moreover,  the  comparison  with  the  pericardial  exudation  shows, 
we  think,  that  the  essential  change  which  produces  the  rheu- 
matic nodule  is  an  actual  deposit  of  inflammatory  exudation ; 
and  one  might  even  go  further  and  say  that  the  formation  of 
fibrous  tissue  is  not  a  necessity  :  it  need  not,  and  certainly 
does  not  always  occur.  This  conclusion,  is  drawn  from  the 
microscopic  appearances,  is  confirmed  by  the  clinical  fact  that 
a  nodule  may  appear  in  twenty-four  to  forty-eight  hours,  and 
the  whole  time  from  appearance  to  disappearance  may,  it 
would  seem,  be  only  three  days. 

Finally,  we  would  suggest,  if  the  occurrence  of  fibrous  tissue 
formation  is  to  be  regarded  as  a  late  phenomenon  and  in  no 
way  essential  to  the  formation  of  nodules,  a  view  which  we 
think  is  confirmed  by  the  appearance  we  have  described, 
that  it  is  more  satisfactory  to  apply  the  term  "  rheumatic  " 
or  "  subcutaneous  "  to  these  nodules  than  to  call  them 
"  fibrous." 

1  Later  investigations  lead  us  to  modify  this  statement  and  to 
substitute  as  the  essential  element  of  the  nodule  the  deposit  of  the 
diplococci  in  the  tissue.  We  would  also  add  to  this  description  that 
necrosis  of  tissue  as  well  as  fibrino-cellular  exudation  occurs  in  the 
centre  of  the  nodule. 


PAPER  NO.  VII 

A  CASE  OF  VIRULENT  ACUTE  RHEUMATISM 
WITH  EXTENSIVE  PURPURA;  TEMPO- 
RARY IMPROVEMENT  FOLLOWED  BY 
DEATH  FROM  CARDIAC  FAILURE ;  NE- 
CROPSY ;    MICROSCOPY 

(Under  the  care  of  Dr.  D.  B.  Lees.) 
(Reprinted  from  the  Lancet,  October  28,  1899.) 

The  case  recorded  in  this  paper  was  a  very  remarkable  one,  and  at 
the  time  of  its  occurrence  gave  valuable  indications  of  the  direction  for 
further  research.  The  isolation  of  streptococci  from  the  blood  during 
life,  with  the  discovery  of  the  endocardial  lesions  of  simple  rheumatic 
endocarditis  after  death,  supplied  the  first  definite  evidence  we  had 
met  with  supporting  the  view  that  rheumatism  might  cause  both  a 
simple  and  malignant  endocarditis.  This  case  also  added  support 
to  previous  studies  of  the  myocardium,  and  finally  brought  prominently 
before  us  the  possibility  that  the  bacterial  agent  we  were  searching  for 
in  acute  rheumatism  was  a  strepto-diplococcus. 

A  girl,  aged  17  years,  was  admitted  to  St.  Mary's  Hospital 
on  January  16,  1899,  for  purpura  and  shortness  of  breath. 
On  the  morning  of  the  13th  she  had  noticed  some  purple 
spots  about  both  ankles,  followed  on  the  next  day  by  pains 
in  the  joints.  Upon  close  inquiry  it  was  ascertained  that 
on  the  9th  the  throat  had  been  sore  and  that  on  the  15th 
there  had  been  a  shivering  attack.  The  important  facts 
in  her  previous  history  were  an  attack  of  chorea  five  years 
and  an  attack  of  rheumatic  fever  two  years  previously. 

Upon  admission  it  was  evident  that  the  patient  was  seriously 
ill  ;  the  face  was  flushed,  the  temperature  was  ioi.6c  F.,  and 
the  pulse-rate  was  120  to  the  minute.  She  complained  of 
slight  pains  in  both  ankle-joints  and  the  left  knee  and  these 

84 


VIRULENT  RHEUMATISM  WITH  PURPURA       85 

joints  were  swollen.  Both  lower  extremities  were  covered 
with  purpuric  patches  of  varied  size  and  upon  the  outer  sides 
of  the  legs  there  were  erythematous  areas  indicative  of  a  fresh 
outbreak  of  purpura  in  these  positions.  The  pulse  was  regular 
and  easily  compressible.  The  cardiac  impulse  could  not  be 
seen  but  was  felt  in  the  fifth  intercostal  space  almost  in  the 
anterior  axillary  line.  The  percussion  limits  of  the  deep 
cardiac  dullness  were  as  follows  :  two  and  a  half  fingers' 
breadth  external  to  the  left  vertical  nipple  line  and  two  fingers' 
breadth  external  to  the  right  sternal  margin,  the  upper  limit 
being  the  third  rib.  There  was  no  pericardial  friction,  but 
over  the  region  of  the  impulse  there  were  systolic  and  presystolic 
murmurs.  The  aortic  second  sound  was  clear  but  the  systolic 
murmur  audible  over  the  region  of  the  impulse  could  be  traced, 
though  with  diminishing  intensity,  to  the  tricuspid,  pulmonary, 
and  aortic  areas.  In  the  left  axilla  there  was  pleural  friction 
and  there  were  scattered  rales  in  both  lungs.  The  urine  was 
free  from  albumin  and  blood.  Neither  the  liver  nor  the 
spleen  could  be  felt.  To  summarise  briefly  the  condition, 
it  represented  the  features  of  a  severe  attack  of  rheumatism  in 
a  patient  who  was  already  predisposed  to  the  disease,  the 
special  clinical  interest  being  the  marked  cardiac  dilatation 
and  extensive  purpura.  The  day  after  admission  a  sore 
throat  again  developed  and  then  the  purpura,  though  fading 
upon  the  legs,  appeared  upon  the  elbows  and  forearms.  The 
pleural  friction  remained  constant  and  the  cardiac  dilatation 
increased.  The  line  of  treatment  that  was  adopted  was 
application  of  the  ice-bag  over  the  heart  when  pericarditis 
appeared  and  the  administration  of  salicylate  and  bicarbonate 
of  soda. 

During  the  next  week  some  dullness  was  discovered  at  the 
base  of  the  left  lung  and  the  purpura  became  much  more 
extensive  over  the  arms  and  also  appeared  upon  the  face  and 
abdomen.  The  patient  was  now  looking  very  ill  and  was 
wasting  considerably.  The  temperature  was,  however,  never 
high,  -seldom  reaching  1010.  On  January  24,  eight  days 
after  admission,  general  pericardial  friction  developed  and 
during  the  next  few  days  the  purpura  spread  over  the  abdomen 
and  backand  became  so  extensive  as  to  baffle  description. 
In  many  places  there  were  large  sanious  bullae  and  over  the 
back  the  epidermis  began  to  give  way,  leaving  raw  and  painful 


86  VIRULENT  RHEUMATISM  WITH 

surfaces.  During  this  week  the  liver  rapidly  enlarged  and 
reached  the  umbilicus,  the  respiration  rate  rose  from  28  to 
48  per  minute,  the  lungs  were  congested,  and  a  fatal  termina- 
tion appeared  to  be  imminent.  Venesection  was  resorted  to 
for  the  relief  of  the  right  heart  failure,  and  cultivations,  aerobic 
and  anaerobic,  were  made  by  Mr.  Plimmer  and  Dr.  Poynton 
of  the  blood  taken  from  the  median  basilic  vein  with  every 
precaution.  Upon  two  occasions  a  pure  growth  of  cocci 
arranged  in  chains  was  obtained.  In  one  of  the  anaerobic 
tubes  a  bacillus  was  also  present  but  Dr.  Poynton  failed  to 
isolate  it.  It  was  a  point  of  some  interest  that  where  carbolic 
compresses  had  been  used  to  the  arm  for  antiseptic  preparation 
purpura  rapidly  appeared  and  was  very  marked,  whereas 
cotton-wool  wrapped  round  the  tender  joints  produced  no  such 
effect.  The  fluid  from  the  bullae  gave  a  growth  of  staphylococci 
Examination  of  the  blood  showed  no  leucocytosis  of  note. 

The  pericarditis  remained  evident  for  the  next  three  weeks, 
the  extent  of  the  friction  gradually  diminishing.  Throughout 
this  period  the  patient  was  extremely  ill,  the  legs  became 
cedematous,  the  purpura  still  further  increased,  and  there  was 
orthopncea  with  great  prostration.  By  the  middle  of  February 
there  was  slight  improvement,  the  temperature  rarely  reached 
ioo°,  and  the  cardiac  inflammation  slowly  diminished.  Digitalis 
and  nux  vomica  were  now  given  and  the  improvement  was 
steadily  maintained.  At  this  time  the  most  noticeable  sj'mp- 
toms  were  attacks  of  dyspnoea  and  blueness,  with  paroxysms 
of  precordial  pain.  B}*  the  end  of  March  there  was  a  distinct 
gain  in  every  way,  the  purpura  had  subsided,  the  skin  was 
healing,  and  the  oedema  had  disappeared.  Good  sleep  was 
obtained,  and  though  the  area  was  still  verjr  extensive  the 
cardiac  sounds  had  become  more  defined.  During  April 
the  patient  was  able  to  lie  upon  a  couch  daily,  but  it  was 
evident  that  she  was  not  gaining  flesh,  as  was  hoped,  and  she 
complained  occasionally  of  the  old  pain  over  the  precordial 
region.  There  was  no  evidence  of  a  relapse  of  rheumatism 
and  no  more  purpura  developed,  but  it  seemed  rather  that 
the  damage  to  the  heart  had  been  so  severe  and  the  circulatory 
power  so  enfeebled  that  the  nourishment  of  the  tissues  could 
barely  be  maintained  even  at  this  low  level.  On  April  12,  the 
pulse  became  irregular  and  there  was  troublesome  vomiting. 
The  liver  rapidly  enlarged  and  the  venous  congestion  increased. 


EXTENSIVE  PURPURA  87 

The  patient  lingered  on  for  a  few  days  and  then  died  almost 
suddenly  on  the  15th  from  cardiac  failure. 

A  post-mortem  examination  was  made  24  hours  after 
death.  The  heart  was  much  dilated  and  the  left  lung  was 
collapsed  and  lay  hidden  behind  the  left  ventricle.  The 
pericardium  was  adherent,  the  adhesions  being  of  recent 
date.  Although  the  area  of  precordial  dulness  had  been 
so  extensive  yet  there  was  no  fluid  in  the  pericardial  sac, 
this  being  obliterated  by  the  general  adhesion.  The  right 
limit  of  the  heart  occupied  by  the  right  auricle  did  not  when 
traced  downward  curve  inward  at  its  lower  part  to  join 
the  right  ventricle,  as  is  normally  the  case,  but  extended  in 
a  straight  line  to  the  diaphragm.  This  is  a  fact  of  some 
importance,  for  the  inward  curve  of  the  right  border  of  the 
cardiac  dullness  has  been  looked  upon  by  some  authorities  as 
a  useful  assistance  in  distinguishing  between  pericardial 
effusion  and  cardiac  dilatation..  When,  however,  there  is 
great  dilatation  of  the  heart  this  cannot  be  relied  upon,  for 
on  this  and  several  other  occasions  Dr.  Poynton  has  observed 
this  alteration  in  the  contour  of  the  auricle.  The  cardiac 
muscle  was  profoundly  altered  and  of  a  pale  purple  colour. 
The  mitral,  aortic,  and  tricuspid  valves  were  all  slightly 
thickened,  the  mitral  to  the  most  marked  extent.  There 
was  no  recent  valvulitis;  and  there  was  rigidity  rather  than 
stenosis  of  the  mitral  orifice.  In  the  first  part  of  the  aorta 
there  were  some  patches  of  aortitis  and  there  was  a  small 
infarct  in  the  spleen.  The  remaining  viscera  showed  the 
changes  usually  observed  in  severe  cardiac  failure.  The 
pleurae  contained  no  excess  of  fluid  but  on  either  side  there 
were  recent  pleuro-pericardial  adhesions. 

Sections  of  the  heart  walls  were  made  in  several  situations 
and  some  of  the  tissues  were  fixed  in  perchloride  of  mercury 
and  others  in  Hermann's  fluid.  Throughout  the  entire  wall, 
including  the  papillary  muscles,  there  was  extensive  fatty 
change  in  the  muscle  fibres.  Scattered  through  the  heart 
wall  {here  was  also  a  cellular  exudation  between  the  muscular 
bundles,  which,  though  not  extensive,  was  definite.  A  very 
striking  feature  in  the  sections  was  great  capillary  dilatation, 
and  though  the  capillaries  are  more  than  usually  apparent 
in  fatal  cases  of  actue  rheumatism  this  condition  was  remark- 
able. 


88  VIRULENT  RHEUMATISM  WITH 

Considered  from  the  standpoint  of  the  relation  of  rheumatism 
to  infective  endocarditis  this  case  is  of  some  considerable 
interest.  The  extraordinary  purpura  pointed  to  a  profound 
alteration  in  the  blood  such  as  occurs  in  septic  rather  than 
in  rheumatic  conditions  and  the  cultivations  of  streptococci 
from  the  blood  also  supported  this  view.  But  the  clinical 
course  was  that  of  virulent  rheumatism  and  the  necropsy 
showed  results  which  are  associated  with  rheumatic  rather 
than  infective  endocarditis.  It  is  in  such  a  case  as  this  that 
the  difficulties  in  separating  these  two  conditions  become 
apparent.  If  rheumatism  be  the  result  of  a  specific  micro- 
organism may  it  not  be  that  infective  endocarditis  now  and 
again  represents  some  phase  of  that  specific  rheumatic  infection 
in  which  the  virulence  has  become  exalted  or  the  resistance 
altered  in  some  unusual  manner  ?  A  very  clear  picture  can 
be  imagined  of  an  alcoholic  patient  becoming  the  victim  of 
tuberculosis,  but  it  is  more  difficult  to  apply  this  principle  of 
secondary  infection  to  rheumatism  and  infective  endocarditis, 
for  the  former  disease  may  produce  endocarditis,  infarction, 
purpura,  sweating,  and  fever,  and  the  latter  need  not  necessarily 
produce  suppuration. 

Again,  apart  from  the  extreme  purpura,  this  case  presents 
features  of  interest  as  an  example  of  virulent  rheumatism. 
Thus,  pericarditis  did  not  become  manifest  until  eight  days 
after  admission,  yet  from  the  first  the  cardiac  dilatation 
pointed  to  a  fresh  rheumatic  infection.  No  doubt  pericarditis 
may  exist  before  detection  by  the  friction,  but  it  may  well  be 
doubted  after  the  study  of  such  a  case  as  this  whether  dilatation 
which  so  commonly  precedes  rheumatic  pericarditis,  is  to  be 
explained  by  any  latent  pericardial  inflammation.  That 
there  is  slight  pyrexia  in  severe  rheumatic  affections  of  the 
heart  is  a  well-recognised  clinical  phenomenon  and  of  much 
interest  now  that  fever  is  more  and  more  looked  upon  as  an 
evidence  of  reaction  to  infections.  The  enfeebled  circulation 
may  have  some  profound  influence — a  chemical  one — in 
preventing  this  reaction  :  a  condition  perhaps  comparable 
to  the  low  temperature  and  feeble  heart  of  the  pneumonia  in 
alcoholism  and  to  the  last  stages  of  severe  septicaemia.  The 
attacks  of  precordial  pain  during  the  period  of  improvement 
were  compatible  with  a  severe  myocardial  affection,  and  the 
necropsy  proved  that  it  could  not  be  due  to  a  previously 


EXTENSIVE  PURPURA  89 

thickened  and  generally  adherent  pericardium.  The  marked 
fatty  degeneration  of  the  muscular  fibres  has  doubtless  an 
important  meaning.  This  change  in  the  cardiac  muscle  is 
frequently  regarded  as  due  to  an  impaired  circulation.  It 
is,  however,  much  nearer  to  the  truth  to  speak  of  it  as  due 
to  a  poisoned  circulation,  for  it  is  found  in  alcoholism,  typhoid 
fever,  diphtheria,  and  in  other  infections.  In  diphtheria  the 
condition  of  the  heart  wall  may  almost  precisely  resemble 
that  found  in  rheumatism,  and  there  is  but  little  doubt  that 
diphtheria  acts  directly  upon  this  structure. 


PART  II 

THESE  PAPERS  DEAL  WITH  THE  DEMONSTRATION 
OF  THE  BACTERIAL  CAUSE  OF  ACUTE  RHEUMA- 
TISM, THE  NATURE  OF  THE  RHEUMATIC  PRO- 
CESSES IN  MAN  AND  ANIMALS,  THE  BEARING 
OF  THE  RESULTS  OBTAINED  UPON  CONDITIONS 
ALLIED  TO  THE  RHEUMATIC,  TOGETHER  WITH 
SOME    INVESTIGATIONS    INTO    SUCH    CONDITIONS 

SUB-GROUP  A 

VIII.  THE  iETIOLOGY  OF  RHEUMATIC  FEVER 

IX.  THE  PATHOGENESIS  OF  RHEUMATIC  FEVER 

X.  THE  INFECTIVITY  OF  ACUTE  RHEUMATISM,  WITH 
SPECIAL  REFERENCE  TO  CHRONIC  ARTHRITIS  AND 
RENAL  DISEASE 


PAPER  NO.  VIII 
THE  ^ETIOLOGY  OF  RHEUMATIC  FEVER 

(Reprinted  from  the  Lancet,  September  22,  1900.) 

This  paper  was  the  result  of  an  investigation  extending  over  two 
and  a  half  years,  during  which  time  Westphal,  Wassermann,  and 
Malkoff  published  their  results  from  the  investigation  of  a  fatal  case 
of  acute  rheumatism  with  chorea.  Progress  was  slow  for  two  chief 
reasons.  We  had  been  led  by  the  fact  that  Triboidet  had  relegated 
the  position  of  the  diplococcus  which  he  had  investigated  to  a  secondary 
position  in  the  pathogenesis  of  the  disease,  to  commence  with  a  search 
for  Achalme's  bacillus.  During  this  search  we  discarded  on  several 
occasions  the  very  micrococcus  we  now  believe  to  be  the  true  excitant 
of  the  disease.  Then  for  twelve  months  we  failed  to  demonstrate  the 
diplococcus  in  the  human  tissues  and  only  succeeded  when  we  obtained 
experimental  carditis.  Taking  advantage  after  this  of  the  thin  parietal 
pericardium  of  the  rabbit,  we'  were  able  by  suitable  methods  to  look 
along  the  capillary  blood-vessels,  and  thus  trace  the  escape  of  the  micro- 
cocci into  the  tissues  and  study  their  subsequent  fate.  This  paper 
was  the  basis  of  our  subsequent  investigations ,  for  it  was  laid  down  upon 
the  broad  lines  of  clinical,  pathological,  bacteriological,  and  experi- 
mental evidence.  From  the  first  we  recognised  the  pitfall  of  looking 
upon  the  bacterial  cause  of  a  specific  disease,  and  a  specific  test  for  a 
bacterium  in  vitro  as  identical  problems.  At  the  time  of  publication 
the  elementary  conception  of  the  streptococcal  group  added  considerably 
to  the  difficulty  of  combating  the  view  that  we  were  working  with  a 
contamination  or  with  a  secondary  infection. 

The  aetiology  of  rheumatic  fever  has  proved  to  be  a  problem 
of  such  complexity  that  it  is  necessary  to  state  at  the  very 
outset  of  this  paper  the  scope  and  object  of  the  research.  The 
various  results  that  had  been  already  obtained  by  investigators 
were  in  themselves  our  first  difficulty,  for  they  necessitated 
the  employment  of  widely  different  methods  to  enable  us  to 
cover  the  ground  already  traversed.     Our  first  intention  was 

93 


94        THE  AETIOLOGY  OF  RHEUMATIC  FEVER 

to  obtain,  if  possible,  some  definite  facts  from  which  as  a 
basis  we  might  make  further  advances,  and  the  discovery 
and  isolation  of  micro-organisms  in  the  form  of  diplococci  in 
eight  succssive  cases  of  rheumatic  fever  afforded  us  this 
opportunity.  When  we  had  obtained  these  diplococci  in 
pure  culture  Mr.  H.  G.  Plimmer  undertook  a  series  of  inocula- 
tions into  animals  and  the  results  that  followed  provided  us 
with  further  data.  Finally,  microscopic  investigations  of  the 
human  and  animal  tissues  have  been  another  source  from 
which  we  have  obtained  facts  which  we  believe  to  be  of  con- 
siderable importance.  The  methods  that  have  been  used 
and  the  conclusions  that  have  been  obtained  from  these  three 
sources  are  detailed  in  this  paper,  together  with  a  brief  historical 
survey  of  the  work  of  others  upon  this  subject. 

There  are  many  points  of  interest  that  are  suggested  by 
these  results  ;  but  the  most  important  fact  deducible  from 
our  researches,  as  detailed  below,  is  that  this  diplococcus  which 
we  have  isolated  is  a  cause  of  rheumatic  fever.  It  is  to  this  con- 
clusion that  our  results  seem  irresistibly  to  lead.  We  are  not, 
however,  in  the  face  of  the  results  of  others,  in  a  position  to 
state  that  these  diplococci  are  invariably  present  in  rheumatic 
fever,  nor  are  we  able  to  claim  that  they  are  the  only  cause 
of  this  disease. 

An  Outline  of  the  History  of  the  Bacteriology  of 
Rheumatic  Fever 

Before  giving  an  outline  of  our  results  a  historical  survey  of 
the  subject  is  appended  sufficient  to  indicate  the  various 
views  that  are,  and  have  been  held,  and  to  do  justice  to 
others  who  have  made  investigations  upon  this  question.  This 
outline  cannot  claim  to  be  exhaustive,  but  it  does,  we  hope 
give  due  credit  to  those  who  have  already  expended  much 
labour  in  attempting  to  discover  the  true  cause  of  rheumatic 
fever.  Dr.  A.  Mantle  in  1886,  described  and  pictured  a  dip- 
lococcus in  the  blood  of  cases  of  rheumatic  fever,  and  ad- 
vanced the  theory  that  the  disease  was  of  microbic  origin.  In 
1892  Fraenkcl  x  called  attention  to  a  paper  by  P.  Guttmann 
upon  the  aetiology  of  rheumatism  and  its  complications 
Guttmann  described  a  case  of  very  acute  rheumatism  with 
exudative  pericarditis  complicated  by  abscesses  in  the  kidneys 
and  muscles  from  which  the  staphylococcus  pyogenes  flavus 


THE  ETIOLOGY  OF  RHEUMATIC  FEVER        95 

was  isolated.  This  micro-organism  was  obtained  from  the 
pericardial  exudation  and  the  abscesses  but  not  from  the 
joints.  Guttmann  expressly  stated  that  this  was  not  a  case 
of  true  rheumatism,  nor  did  he  consider  this  organism,  if  it 
were  the  cause  of  the  rheumatism  in  this  case,  to  be  the  sole 
cause  of  rheumatic  fever.  Leyden  also  concurred  with  this 
opinion.  In  the  same  year  Sahli 2  discovered  the  staphylococcus 
pyogenes  citreus  in  the  synovial  membrane  of  the  joints  in  a 
case  of  rheumatic  fever  and  also  in  the  pericardial  exudation. 
He  considered  rheumatic  fever  to  be  due  to  a  staphylococcic 
infection  but  left  it  an  open  question  as  to  whether  or  not 
the  condition  was  due  to  an  attenuation  of  the  organism. 
Netter3  also  isolated  a  streptococcus  from  a  case  clinically 
resembling  rheumatic  fever  but  following  acute  suppurative 
otitis  media.  Lanz4  in  1893  published  a  paper  upon  experi- 
mental results  connected  with  suppurative  polyarthritis. 
From  the  pus  of  an  abscess  of  the  brain  operated  on  by  Kocher 
he  isolated  a  bacillus.  This  on  intravenous  injection  into 
rabbits  caused  death  in  23  days.  Suppurative  polyarthritis 
resulted  and  the  bacillus  was  again  isolated  from  the  joint. 
To  this  organism  he  gave  the  name  of  bacillus  pyogenes 
f cetidus  liquefaciens.  In  1894  Maragliano  5  obtained  diplococci 
and  staphylococci  from  a  case  which  commenced  clinically 
as  rheumatic  fever  and  ended  as  a  septicaemia.  This  writer 
also  insisted  upon  the  relationship  between  rheumatic  fever 
and  suppurative  affections.  At  this  time  Chvostek6  and 
Singer7  published  papers  upon  the  micro-organisms  found 
in  the  urine  of  patients  suffering  from  rheumatic  fever.  Singer 
found  as  the  result  of  the  examination  of  the  urine  in  17  cases 
that  the  staphylococcus  pyogenes  aureus  was  frequently 
present,  and  when  present  was  to  be  found  in  considerable 
numbers,  but  became  less  as  the  disease  declined.  He  associated 
this  occurrence  with  the  rheumatic  process.  Chvostek,  though 
recognising  the  importance  of  Singer's  investigation,  doubted 
the  validity  of  his  conclusions.  Dana8  in  1894  isolated  a 
diplococcus  from  a  case  of  chorea  following  rheumatism.  The 
organism  was  found  in  the  meninges  of  the  brain  and  spinal 
cord.  Charrin9  found  streptococci  in  cases  of  rheumatic 
fever.  Sacaze10  made  the  interesting  suggestion  that  some 
external  wound,  often  insignificant,  might  be  the  site  of  in- 
fection in  rheumatic  fever.     In  1896  Lubarsch,11  in  a  paper 


96        THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

upon  the  streptococcus  group  and  the  diseases  caused  by 
them,  alludes  to  an  exhaustive  paper  by  Buss  of  Bremen 
upon  the  relation  of  angina  faucium  to  rheumatic  fever. 
Bu-s12  in  this  paper  came  to  the  conclusion  that  the  throat 
and  intestines  are  in  many  instances  the  sites  of  the  entrance 
of  the  rheumatic  infection. 

The  clinical  importance  of  the  angina  faucium  that  occurs 
in  rheumatism  had  long  been  recognised.  It  was  mentioned 
by  Trousseau13  in  his  "  Clinical  Medicine  "  and  Dr.  Kingston 
Fowler14  in  1880  published  an  account  of  20  cases  of  acute 
rheumatism  ushered  in  by  tonsillitis  ;  Dr.  Cheadle15  further 
insisted  upon  this  clinical  fact  in  1SS8  in  the  Harveian  Lectures 
upon  the  rheumatic  state  in  childhood. 

Achalme16  introduced  a  new  field  for  investigation  by  a 
series  of   papers  upon   the   bacteriology   of   rheumatic   fever 
dating  from  1S91.     He  discovered  a  bacillus  in  the  blood  of 
patients  who  succumbed  to  rheumatic  fever  and  by  his  sub- 
sequent  researches   confirmed   this   observation.     His   results 
are  of  such  importance  that  some  space  must  be  devoted  to 
an  account  of  them.     The  bacillus  resembled  that  of  anthrax 
both  in  size  and  in  the  blunt  ends,  but  varied  considerably 
in  size  though  not  in  thickness  in  different  media.     It  occurred 
in  the  blood  in  scanty  numbers  and  was  grown  anaerobically, 
not  aerobically.     A  mixture   of  milk  and  beef-tea   was  the 
medium  used,  but  it  grew  well  upon  alkaline  bouillon  made 
from  hor=ti'  he-h.     The  anaerobic  tubes  were  not  opened  for 
from  eight  to  ten  day^.     Solid  media  were  not  well  adapted 
for  studying  the  properties  of  this  bacillus.     When  growing 
in  alkaline  bouillon  gas  bubbles  and  a  turbid  deposit  appeared 
within  12  hours.     The  bacillus  stained  well  with  all  the  aniline 
dyes  but  best  with  faintly  alkaline  meth}"lene  blue.     In  1897 
Achalmu17  published  a  detailed  account  of  his  researches  upon 
this  bacillus  with  clinical  histories  of  nine  cases  in  which  it 
had  been  found.     The  results  of  injections  into  animals  were 
also  given.     Sanious  exudation  at  the  sites  of  inoculation  was 
a  prominent  feature  and  in  the  most  severe  cases  death  occurred 
from  septicaemia.     A  true  picture  of  rheumatic  fever,  as  it 
occurs  in  man,  did  not  appear  to  result  in  animals  thus  infected. 
The  results  that  Achalme  obtained  have  naturally  aroused 
considerable  interest,  and  it  is  remarkable  that  an  organism 
of  such  a  -ize  and  one  that  stains  ;0  well  should  ha\e  been 


THE  ETIOLOGY  OF  RHEUMATIC  FEVER         97 

overlooked  by  those  who  have  investigated  the  tissues  in  rheu- 
matic fever. 

Thiroloix,18  following  Achalme's  investigation  of  this  bacillus, 
in  a  series  of  papers  fully  confirmed  his  results.  In  addition, 
in  five  cases  of  rheumatism  he  obtained  this  bacillus  and 
inoculations  into  rabbits  gave  the  entire  picture  of  rheumatic 
fever.  Again,  he  obtained  the  organism  from  the  blood  and 
pleural  effusion  in  one  case  of  rheumatic  fever,  and  this  pro- 
duced in  guinea-pigs  sanious  exudations  and  in  rabbits  a 
heart  but  not  a  joint  inflammation.  In  two  later  cases  he 
obtained  the  latter  also.  Triboulet19  in  a  case  of  rheumatic 
fever  found  a  bacillus  resembling  that  described  by  Achalme. 
But  later  Triboulet  and  Coyon20  found  a  diplococcus  in  five 
cases.  In  two  of  these  the  diplococci  were  associated  with 
Achalme's  bacillus,  and  they  argue  that  severe  and  complicated 
cases  are  due  to  Achalme's  bacillus  together  with  the  associated 
diplococci,  whereas  the  simple  cases  of  rheumatism  are  due 
to  the  diplococci  alone.  Riva21  in  1897  isolated  a  specific  micro- 
organism from  eight  cases  of  rheumatic  fever.  The  organism 
varied  much  in  shape  in  different  media  and  occurred  in  both 
coccal  and  bacillary  forms.  He  made  use  of  a  complicated 
medium  slightly  acid  in  reaction,  an  essential  constituent  of 
which  was  the  synovia  from  the  joints  of  horses.  In  1898 
Apert  and  Triboulet  22  obtained  some  remarkable  results  by 
the  inoculation  of  a  rabbit  with  a  diplococcus  isolated  from  the 
blood  of  a  patient  suffering  from  rheumatic  fever.  Twenty 
days  afterwards  they  found  thickening  of  the  mitral  valve 
with  hypertrophy  and  dilatation  of  the  chambers  of  the  heart 
and  excess  of  clear  fluid  in  the  pericardium.  There  was  also 
pleurisy  but  no  peritonitis.  None  of  the  joints  were  affected. 
This  diplococcus  was  identical  in  character  with  that  found 
in  11  other  cases  of  rheumatic  fever.  In  spite  of  the  absence 
of  any  joint  lesions  Triboulet  considered  this  organism  to  be 
specific.  Injected  under  the  skin  Apert  found  the  diplococcus 
produced  a  local  induration.  Bettencourt23  in  1898  supported 
the  researches  of  Achalme  and  Thiroloix.  Gustav  Singer24 
in  a  monograph  gave  the  results  of  an  extensive  investiga- 
tion of  many  cases  of  rheumatic  fever  and  was  led  to  the 
conclusion  that  acute  rheumatism  is  not  a  specific  disease  but 
owes  its  origin  to  streptococcal  and  staphylococcal  infection. 

In   1889   Kronenberg,25  in  a  paper  upon  angina   faucium 

7 


93        THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

in  acute  rheumatic  fever,  expressed  doubts  that  rheumatism  is 
a  disease  sui  generis,  but  he  thought  rather  that  it  was  a  peculiar 
reaction  of  the  joints  and  other  tissues  to  a  series  of  bacterial 
influences — as,  for  example,  the  gonococcal,  the  streptococcal, 
and  the  allied  infections.  In  1899  Westphal,  Wassermann, 
and  Malkoff  published  a  paper,  "  Ueber  den  Infectiosen 
Charakter  und  den  Zusammenhang  von  Acutem  Gelenkrheu- 
matismus  und  Chorea."26  Westphal  narrated  the  history  of 
the  case  from  which  the  material  was  obtained.  It  was  a 
severe  case  of  chorea  that  followed  acute  rheumatism,  occurring 
in  January  1899.  Violent  delirium  with  hyperpyrexia  and 
collapse  resulted  in  death  on  February  24.  The  necropsy 
a  few  hours  later  showed  minute  vegetations  upon  the  mitral 
valve  and  parenchymatous  nephritis  ;  there  was  no  suppura- 
tion. Cultures  were  made  from  the  heart's  blood,  pericardial 
fluid,  mitral  valve,  spleen,  and  brain.  Wassermann,  after 
alluding  to  the  resarches  of  Loffler,  Michaelis,  Eberth,  Litten, 
and  von  Leyden,  described  the  bacteriological  results.  A 
diplococcus  resembling  morphologically  that  found  by  von 
Leyden  in  rheumatic  valvulitis  was  isolated  and  in  80  rabbits 
produced  fever  and  multiple  arthritis.  This  organism  appeared 
as  a  diplococcus  in  the  tissues  but  grew  in  culture  as  a  strepto- 
coccus. The  number  of  micro-organisms  in  the  tissues  of  the 
patient  was  very  small.  It  required  a  higher  degree  of  alkalinity 
than  that  of  the  ordinary  media,  upon  which  it  refused  to  grow. 
The  incubation  period  was  from  three  to  ten  days.  All  the 
tissues  of  the  joint  were  inflamed  and  in  the  fluid  of  those 
which  had  been  affected  longest  there  was  a  considerable 
number  of  leucocytes.  In  addition  there  was  exudation  in  the 
tendon  sheaths  and  bursas.  The  micro-organism  was  found 
in  the  arthritic  exudation  and  cultures  from  the  animals  repro- 
duced the  disease  in  other  animals.  Litten27  at  the  same 
date  isolated  from  a  malignant  form  of  rheumatic  endocarditis 
(non-suppurative)  a  very  minute  streptococcus  which  was  fatal 
to  mice  and  guinea-pigs  but  rapidly  lost  virulence  upon  culture. 
In  a  footnote  to  his  paper  he  is  of  opinion  that  Westphal  and 
Wassermann  have  probably  found  the  true  excitant  of  acute 
rheumatism  but  suggests  that  there  may  possibly  be  more  than 
one.  It  appears  to  us  that  this  diplococcus  must  resemble, 
if  not  be  identical  with,  that  investigated  by  Triboulet  in  1897. 
This  brief  survey  is   sufficient   to   show  how  complicated 


THE  /ETIOLOGY  OF  RHEUMATIC  FEVER         99 

and  uncertain  the  present  position  of  the  bacteriology  of 
rheumatic  fever  still  remains.  In  the  following  short  analysis 
of  the  various  hypotheses  we  hope  to  make  clear  that  view 
of  the  subject  which  seemed  to  us  the  most  probable  and  to 
indicate  the  direction  in  which  our  researches  tended.  There 
may  be  some  who  still  decline  to  regard  rheumatic  fever  as  a 
microbic  disease,  but  we  have  started  upon  the  assumption 
that  it  is  an  infection,  being  led  to  this  conclusion  by  the 
results  of  clinical  and  pathological  experience  and  teaching. 
The  broad  clinical  view  of  rheumatism  which  has  been  taken 
by  such  authorities  as  Dr.  W.  B.  Cheadle,  Dr.  Thomas  Barlow, 
Dr.  D.  B.  Lees,  and  Dr.  A.  Garrod  in  this  country  appears 
to  us  to  support  this  hypothesis  very  strongly. 

View  No.  1.     Allowing  that  the  cause  of  rheumatic  fever 
is  microbic,  one  view  that  has  met  with  considerable  support 
maintains  that    there  is  no  specific  micro-organism,  but  that 
rheumatism  is  but  a  form  of  septicaemia  which  owes  its  origin 
to    staphylococcal    and    streptococcal    infection.     The    close 
analogy  between  the  rheumatic  processes  and  those  of  pyaemia 
and  the  frequent  discovery  of  staphylococci  and  streptococci 
in  cases  of   rheumatic   fever  have  naturally  led  to  this  view. 
It  is  undoubtedly  a  very  important  one  and  involves  bacterio- 
logical and  clinical  problems  of  the  greatest  difficulty.     It  raises 
the  question  of  what  is '  really  the  definition  of  the  specificity 
of  an  organism  and  deals  with  what  is  still  an  unknown  quantity 
— viz.,  the  extent  of  variability  that  is   possible  in  a  micro- 
organism and  its  results  under  varying  conditions  of  virulence 
and  resistance.     We  have  fallen  back  upon  the  teaching  of 
clinical  medicine  and  pathology  as  our  guide  in  this  matter. 
Rheumatic  fever  as  we  meet  with  it  in  England  is  a  common 
disease  with,  on  the  whole,  very  definite  characteristics.     How- 
ever virulent  the  disease  it  may  be  practically  asserted  from 
the    clinical    standpoint    that    suppuration    does    not    occur. 
Many  cases  die  in  the  course  of  a  year  with  acute  cardiac  in- 
flammation, yet  the   heart   and  other  viscera   do   not   show 
abscesses.     We  were  inclined  to  expect  that  an  organism  the 
cause  of  rheumatic  fever  if  isolated  and  inoculated  into  suitable 
animals  would  produce  in  them  a  condition  resembling  the 
rheumatic   fever  of   man  in  the  absence   of   multiple   foci  of 
suppuration.     That  this  limit  may  be  overstepped  both  in 
man   and   animals    under   exceptional,    and    perhaps   as   yet 


ioo       THE  ETIOLOGY  OF  RHEUMATIC  FEVER 

unknown,  circumstances  seemed  to  us  very  probable,  but  the 
general  and1  average  result  that  we  expected  was  a  condition 
in  which  the  absence  of  suppuration  would  be  a  prominent 
feature. 

View  No  2.  Another  view  maintains  that  the  cause  of 
rheumatism  is  a  specific  diplococcus.  It  is  to  this  view  that 
we  inclined,  though  we  would  repeat  once  more  that  the 
definition  of  what  is  meant  exactly  by  "  specific  "  involves 
many  difficult  problems  concerned  with  the  virulence  of  the 
infection  and  nature  of  resistance. 

View  No.  3.  A  third  view  maintains  that  the  cause  is  a 
specific  bacillus.  This  view  is  a  decidedly  simpler  one,  if  it 
were  proved  to  be  true.  If  the  bacillus,  as  for  example,  that 
described  by  Achalme,  be  found  to  be  invariably  present  in 
rheumatic  fever  it  is  easily  distinguishable  from  the  staphy- 
lococci and  streptococci  that  are  found  so  frequently  associated 
in  rheumatism,  and  its  morphological  characters  alone  would 
be  of  the  greatest  assistance  in  establishing  the  truth  of  its 
claim. 

View  No.  4.  A  fourth  view  raises  the  question  of  a  mixed 
infection  of  bacilli  and  micrococci,  an  analogy  to  winch  is 
readily  supplied  by  diphtheria.  To  us  this  view  appeared  one 
of  great  difficulty  and  withal  unsatisfactory.  There  can  be 
no  reasonable  doubt  in  the  face  of  the  numerous  investiga- 
tions that  have  been  made  that  micrococci  of  some  form  or 
other  are  frequently  present  in  rheumatic  fever  and  hence  the 
origin  of  such  a  view  as  the  one  under  consideration.  Nor 
can  there  be  reasonable  doubt  that  they  are  capable  of  pro- 
ducing polyarthritis,  valvulitis,  pericarditis,  pyrexia,  sweating, 
infarction,  and  other  manifestations  closely  resembling  those 
of  rheumatic  fever.  If  then,  both  the  bacilli  and  micro- 
cocci are  needful  to  produce  rheumatic  fever  the  association 
must  be  a  mysterious  one.  If  the  micrococci  are  the  cause  of 
the  symptoms  it  is  possible  that  they  are  restrained  from 
causing  suppuration  by  the  presence  of  the  bacilli.  If  the 
bacilli  are  the  cause  of  the  symptoms  it  is  possible  that  they 
produce  them  only  when  associated  with  these  micrococci, 
though  this  is  difficult  to  realise  when  it  is  remembered  that 
the  latter  may  themselves  produce  almost  similar  lesions. 

View  No.  5.  This  last  view  holds  that  rheumatic  fever  is 
not  a  disease  sui  generis  but  a  particular  reaction  of  the  tissues 


THE  AETIOLOGY  OF  RHEUMATIC  FEVER       101 

to  varied  infections.  We  thought  that  the  remarkable  con- 
stancy of  the  clinical  symptoms  of  rheumatic  fever,  as  met  with 
certainly  in  England,  were  much  against  its  being  a  condition 
that  would  result  from  many  and  varied  infections. 

Not  only  is  there  this  diversity  of  opinion  regarding  the 
organism,  but  opinions  differ  also  as  to  the  explanation  of 
the  way  in  which  the  symptoms  are  caused.  Does  the  micro- 
organism remain  localised  to  one  spot — for  example,  the 
tonsils — and  pour  its  toxins  into  the  system,  giving  rise  in 
this  way  to  carditis,  arthritis,  nodules,  and  other  local  lesions  ? 
or  is  it  widely  distributed  and  present  in  the  local  lesions  ?  We 
inclined  to  the  belief  that  the  organism  was  to  be  found  in  the 
local  lesions,  though  perhaps  only  with  great  difficulty.  The 
probability  of  its  occurrence  at  these  sites  seemed  to  us  to  be 
indicated  by  the  analogy  of  pyaemia. 

To  summarise  our  point  of  view  at  the  start  of  this  investiga- 
tion we  thought  it  most  probable  that  the.  organism  would 
always  be  present  in  cases  of  rheumatic  fever  ;  that  it  would 
be  capable  of  isolation  ;  that  it  would  produce  the  symptoms 
of  rheumatic  fever  in  a  suitable  animal  ;  and  that  it  would 
probably  exhibit  some  definite  peculiarities  upon  culture.  We 
also  thought  that  it  would  be  present  in  the  local  lesions  and 
that  the  infection  would  be  a  simple  and  not  a  mixed  one. 
The  analogy  that  there  appears  to  be  between  rheumatic 
fever  and  septic  infections  pointed  to  the  infection  being 
micrococcal  rather  than  bacillary.  We  were,  however, 
naturally  influenced  by  the  positive  results  of  Achalme  and  his 
corroborators,  and  their  results  appeared  to  us  so  definite  that 
we  gave  especial  attention  to  the  discovery  of  this  bacillus  in 
our  earlier  cases. 

The  Outline  of  the  Investigation 

After. this  brief  consideration  of  these  various  theories  we 
give  in  outline  the  results  of  our  investigation,  then  in  detail 
the  methods,  cases,  and  bacteriological  investigations,  and 
finally  a  short  summary  of  the  facts  which  have  been  established 
with  some  concluding  remarks. 

In  January  1899,  we  undertook  the  study  of  the  bacteriology 
of  rheumatism  with  the  intention  of  confirming,  if  possible, 
the  results  obtained  by  Achalme.  For  some  long  time  we 
were  influenced  by  this  intention,  but  finally  abandoned  the 


102        THE  ETIOLOGY  OF  RHEUMATIC  FEVER 

attempt,  having  failed  to  obtain  a  bacillus  morphologically 
resembling  anthrax  either  in  culture  or  in  the  tissues.  On 
the  other  hand,  we  obtained  later  in  eight  successive  cases 
a  diplococcus  which  grew  in  liquid  media  in  streptococcal 
chains.  This  organism  did  not  thrive  upon  ordinary  agar  or 
serum  agar,  and  though  we  were  able  to  grow  it  eventually 
upon  blood  agar  it  appeared  to  grow  best  in  a  liquid  medium 
of  milk  and  bouillon  rendered  slightly  acid  with  lactic  acid. 
Upon  three  occasions  we  isolated  the  organism  in  pure  culture 
from  the  blood  of  patients  during  life  who  were  suffering  from 
acute  rheumatic  pericarditis.  It  was  also  obtained  from  the 
pericardial  fluid  after  death  and  from  the  cardiac  valves  and 
lastly  from  the  throat  of  a  rheumatic  patient.  In  our  first 
two  cases  we  did  not  investigate  the  characteristics  of  the 
diplococcus  and  in  one  recent  case  it  was  associated  with 
numerous  small  bacilli.  In  one  case  a  sarcina  was  present  as  a 
contamination.  In  five  of  the  eight  cases  it  was  in  pure  culture. 
When  we  became  acquainted  with  the  researches  of  Wasser- 
mann,  Westphal,  and  Malkoff,  it  seemed  clear  that  this  was 
the  organism  they  had  described,  and  we  feel  no  doubt  that 
it  is  identical,  although  there  have. been  certain  differences  in 
the  results  that  we  have  obtained.  As  stated  above,  we 
succeeded  best  in  cultivating  it  in  an  acid  medium  and  have 
not  had  success  with  a  strongly  alkaline  medium,  as  recom- 
mended by  Wassermann,  though  we  are  in  doubt  as  to  the 
exact  degree  of  alkalinity  that  Professor  Wassermann  found 
to  be  most  suitable,  about  which  point  he  made  no  definite 
statement  of  which  we  are  aware.  It  is  of  considerable  interest 
that  we  succeeded  in  growing  the  diplococcus  on  two  occasions 
in  the  pericardial  exudation  and  noticed  in  one  of  these  instances 
an  increase  in  flakiness  of  the  fluid.  On  both  these  occasions 
the  pericardial  fluid  was  distinctly  acid,  so  that  there  is  this 
proof  that  the  organism  will  grow  in  an  acid  medium.  The 
demonstration  of  these  diplococci  in  films  from  the  pericardial 
fluid  after  incubation  is  very  definite,  and  we  have  also  found 
them  in  scanty  numbers  in  films  from  recent  vegetations,  from 
unincubated  pericardial  fluid,  from  blood  from  the  heart,  and 
from  the  throat.  Their  demonstration  in  the  tissues  is  by  no 
means  easy.  We  have  however,  demonstrated  them  un- 
mistakably in  the  tissue  of  a  rheumatic  nodule  and  in  the 
valves,  pericardium,  and  tonsil.     Mr.  H.  G.  Plimmer  under- 


THE  ^ETIOLOGY  OF  RHEUMATIC  FEVER        103 

took  a  series  of  inoculations  for  us  from  the  pure  cultures  that 
had  been  obtained  and  made  intravenous  inoculations  into 
rabbits  with  results  of  which  the  following  is  an  outline. 

The  pericardial  fluid  from  Case  4,  that  of  a  boy  who  had 
died  from  an  exacerbation  of  rheumatism,  gave  the  first  positive 
result.     Three  days  after  inoculation  the  animal  limped  upon 
the  left  fore  leg,  the  left  shoulder- joint  was  swollen,  and  the 
animal  had  lost  flesh.     Later  the  right  hip-joint  and  right- 
shoulder- joint  became  affected,   wasting  continued,  and  the 
rabbit    died    10    days    after    inoculation.     The    post-mortem 
examination  shenved  excess  of  clear  fluid  in  the  right  shoulder- 
joint  and  right   hip-joint   with  reddening  of  the   cartilages. 
The    left    shoulder- joint    contained    an    opaque    fluid    which 
microscopically  contained  numerous  endothelial  cells  and  a 
few  leucocytes.     The  heart  appeared  larger  than  natural,  there 
was  an  excess  of  clear  fluid  in  the  pericardium,  but  apparently 
no  evidence  of  pericarditis  or  endocarditis.     The  liver  w7as 
dark  red.     In  the  lungs  there  wTere  patches  of  broncho-pneu- 
monia.    There  was  no  sign  of  abscess  formation  in  any  of  the 
viscera.     The  clear  fluid  from  the  joints  taken  with  every 
precaution,  was  inoculated  into  milk  tubes.     Films  were  also 
made   and   a   diplococcus  was   demonstrated   and   cultivated 
from  this  clear  fluid.     It  was  also  demonstrated  in  the  mitral 
valve.     Thus  it  will  be -seen  that  in  some  respects  our  results 
in  this  case  corresponded  exactly  with  those  of  Wasserman. 
A  polyarthritis  had  resulted  and  the  joint  first  affected  con- 
tained a  fluid  in  which  there  were  fibrin  and  some  excess  of 
leucocytes,  the  cartilages  of  the  affected  joints  were  redder 
than  normal,  and  in  none  of  the  viscera  were  there  any  foci 
of  suppuration.     In  one  respect  there  was  a  difference  and 
this  was  an  important  one  :  we  had  demonstrated  the  organism 
in  the  mitral  valve.     A  second  rabbit  w7as  inoculated  from  a 
culture  of  the  joint  fluid.     The  cultivations  upon  six  blood 
agar    tubes    were    injected    intravenously   into    this    rabbit 
with  the  following  results.     Upon   the  third   day    the  right 
knee-joint  swelled  and  the  animal  had  lost   160  grammes  in 
w7eight,  then  followed  in  succession  the  other  knee-joint  and 
the  left  shoulder-joint,  and  finally  all  the  larger  joints  became 
implicated.     The  identity  of  the  course  of  the  disease  with 
that  in  the   first   case   w7as  remarkable   and  certain  further 
results  developed.     Seventeen   days  after  the  inoculation   a 


104       THE  ^ETIOLOGY  OF  RHEUMATIC  FEVER 

systolic  murmur  was  detected  at  the  base  of  the  heart  somewhat 
superficial  in  character  and  the  heart  was  acting  with  great 
rapidity.     This  murmur  was  detected  for  two  days  and  then 
was   lost   and  at   the   same  time   the   heart   sounds   became 
faint.     We   diagnosed   pericarditis  with  subsequent   effusion. 
The  next  day  the  animal  died.     During  the  last  week  of  the 
illness  all  the  joint  swellings  had  disappeared  except  that  of 
the  right  knee.     The  necropsy  showed  an  excess  of  clear  fluid 
in  the  pericardium  and  a  fibrinous  coagulum  in  the  sac  with 
some  roughening  of  the  visceral  layer  over  the  large  vessels. 
The  right  knee  was  full  of  an  opaque  fluid  which,  as  in  the 
first    case,    contained   the    diplococci,    endothelial    cells,    and 
leucocytes.     There  was  some  excess  of  fluid  in  the  other  joints 
but  this  was  clear.     Upon  the  mitral  valve  there  were  two 
small  white  opacities  resembling  an  early  granulation.     The 
liver  was  dark  red  and  contained  some  small  white  areas  which 
were  quite  firm  and  slightly  raised.     The  spleen  and  kidneys 
were  pale  but  otherwise  natural.     The  tonsils  were  natural. 
Microscopic  examination  of  the  mitral  valve  did  not  confirm 
the  suspicion  of  endocarditis.     The   opaque   patches  in  the 
liver   proved  to   be  localised  areas   of   coagulation   necrosis. 
There  was  no  trace  of  suppuration  in  the  viscera.     The  myo- 
cardium showed  well-marked  fatty  changes  in  the  fibres  com- 
parable to  the  changes  demonstrated  in  the  human  heart  as 
occurring  frequently  in  acute  rheumatic  carditis.     The  culture 
of  the  organism  was  repeated  as  before  and  the  cultivations 
upon  three  tubes  injected  into  a  third  rabbit,  but  with  a  negative 
result.     The  cultivations  upon  six  tubes  injected  into  a  fourth 
rabbit  resulted  as  follows.     Four  days  after  the  inoculation  the 
right  knee-joint  swelled  and  subsequently  the  right   carpal 
joint  and  left  knee-joint  also  and  there  was  general  wasting. 
Upon  the  tenth  day  we  detected  a  soft  murmur  which  next 
day  we  localised  as  mitral  ;    this  disappeared,   but  on   the 
fourteenth  day  there  was  a  murmur  upon  the  right  side  which 
we  diagnosed  to  be  tricuspid  in  origin.     The  confirmation  of 
these  diagnoses  being  a  matter  of  great  importance  upon  the 
same  day  that  the  tricuspid  murmur  was  detected  the  animal 
was  killed.     The  necropsy  showed  that  two  joints  contained 
an  opaque  fluid  comparable  to  that  found  in  the  preceding 
cases  and  one  a  considerable  quantity  of  clear  fluid.     There 
was  excess  of  clear  fluid  in  the  pericardium.     The  mitral  valve 


V 


FIG.  13 

A  fragment  of  the  parietal  pericardium   stretched  in  a  film  on  a  slide   and  dried, 

stained  and  cleaved,  showing  a  blood-vessel   in   the  parietal  pericardium  of  a  rabbil 

dead  of  carditis.     (Zeiss,  olrj.  ,',,,  oc.  3  I. 

A.  Blood-vessel. 

B.  Wall  of  the  vessel. 

C.  Pericardial  tissue  external  to  the  vessel. 
Diplococci  are  seen  in  each  position. 


THE  .ETIOLOGY  OF  RHEUMATIC  FEVER       105 

showed  a  condition  macroscopically  comparable  to  that  of  an 
early  rheumatic  endocarditis,  and  the  tricuspid  valve  showed 
also,  in  the  very  earliest  stage,  a  row  of  granulations  along  the 
border.  The  condition  of  the  liver  resembled  that  found  in 
Case  2  and  the  kidneys  also  showed  some  white  slightly  raised 
areas  quite  firm  on  section.  The  tonsils  were  unaffected.  The 
microscopic  examination  showed  points  of  the  greatest  interest. 
In  the  parietal  layer  of  the  pericardium,  stretched  out  and 
stained,  we  found  the  diplococci  following  the  course  of  the 
blood-vessels  in  the  perivascular  lymphatic  spaces.  We 
also  demonstrated  them  in  the  mitral  valve  and — what  by  the 
light  of  subsequent  events  was  especially  noteworthy — we  dis- 
covered them  in  the  kidneys  in  great  numbers.  There  were 
no  suppurative  foci  in  the  viscera. 

The  organisms  were  once  more  isolated  and  injected  intra- 
venously into  a  fifth  rabbit.  This  rabbit  developed  poly- 
arthritis, pericarditis,  pleurisy,  and  pneumonia,  with  slight 
valvulitis.  The  animal  was  killed  at  the  height  of  the  disease 
and  the  especial  point  of  interest  in  the  necropsy  was  the 
macroscopic  appearance  of  the  thoracic  viscera.  There  were 
plastic  pericarditis  and  mediastinitis,  with  plastic  pleurisy 
over  those  parts  of  the  lungs  that  are  contiguous  to  the  peri- 
cardium. The  liver  had  the  mottled  appearance  that  is 
seen  in  a  man  as  a  result  of  severe  and  acute  rheumatic  carditis. 
During  the  illness  the  rabbit  had  passed  urine  which  was 
acid  and  contained  numerous  urates,  granular  casts,  and 
diplococci.  From  the  contents  of  the  bladder  we  isolated  and 
cultivated  the  diplococcus  by  the  usual  methods.  There  was 
also  exudation  into  the  tendon  sheaths  around  the  affected 
joints  and  the  connective  tissue  near  the  larger  joints  had 
the  gelatinous  appearance  of  the  nodule  in  man.  We  demon- 
strated the  diplococci  in  the  valves,  pericardium,  joint 
exudate,  liver,  kidneys,  connective  tissues  around  the  joints, 
and  in  large  numbers  in  the  lungs  and  pleurae.  It  is,  we 
think,  impossible  not  to  recognise  in  this  case  the  extra- 
ordinary similarity  to  the  most  severe  types  of  rheumatic 
fever  in  childhood. 

Another  case  in  which  some  remarkable  results  occurred 
was  the  second  of  those  in  which  we  obtained  a  pure  culture 
of  the  diplococcus  from  the  blood  of  a  living  patient  suffering 
from  rheumatic  pericarditis.     The  organism  was  grown  upon 


io6      THE  ETIOLOGY  OF  RHEUMATIC  FEVER 

the  acid  medium  and  transferred  to  blood  agar.  Intravenous 
inoculation  of  a  rabbit  produced  the  following  symptoms. 
Four  days  after  inoculation  the  rabbit  had  begun  to  waste 
and  limped  upon  the  right  hind  leg,  and  the  knee-joint  became 
swollen.  This  continued  for  a  week,  the  animal  still  wasting, 
but  then  it  improved  so  much  that  the  limp  disappeared. 
The  heart  all  this  time  acted  very  rapidly  but  there  was  no 
murmur.  Five  weeks  after  this  there  was  a  relapse  and  both 
the  hind  legs  became  very  weak  and  the  animal  very  emaciated. 
There  did  not  appear  to  be  any  joint  swelling  at  this  time.  This 
condition  continued  for  about  three  weeks  and  then  gradually 
passed  off,  and  no  cardiac  murmur  was  detected  at  any  time. 
Was  this  a  paralytic  phenomenon  ?  It  was  a  natural  sugges- 
tion that  it  might  be  chorea,  but  if  so,  there  was  not  the 
slightest  twitching,  only  great  weakness  of  both  lower  ex- 
tremities that  gradually  passed  away. 

A  third  case  which  produced  an  experimental  result  was 
that  of  Case  6.  The  case  was  one  of  severe  rheumatic  carditis 
with  early  pericarditis.  Associated  with  the  diplococci  there 
were  scfme  short  bacilli  and  the  growth  in  the  pericardial  fluid 
was  accompanied  by  an  offensive  odour.  An  inoculation  of 
the  two  organisms  into  a  rabbit  proved  negative.  An  inocu- 
lation of  the  diplococci  only  into  another  rabbit  also  proved 
negative.  We  were  surprised  at  this  result  and  three  weeks 
later  a  third  attempt  was  made,  though  we  felt  very  doubtful 
that  any  result  would  be  obtained  because  of  the  difficulty  of 
maintaining  the  virulence  of  the  organism.  This  rabbit 
remained  apparently  well,  but  three  weeks  afterwards  we 
found  the  temperature  raised  and  a  definite  systolic  murmur 
at  the  apex.  There  was  no  arthritic  change,  but  the  murmur 
remained  constant  for  a  week  and  was  more  definite  than 
any  that  we  had  previously  heard.  The  animal  was  then 
killed  and  the  tricuspid  and  mitral  valves  were  found  to  be 
inflamed.  There  was  also  a  moderate  quantity  of  clear  fluid 
in  the  abdominal  cavity.  We  demonstrated  the  organisms 
in  the  valves  and  in  the  parietal  pericardium,  throughout  which 
there  was  a  definite  cellular  exudation. 

The  next  case  (Case  7)  gave  a  negative  result,  but  at  this 
we  were  not  surprised,  for  the  pericardium  was  totally  adherent, 
and  though  we  obtained  the  diplococci  from  the  granulations  of 
the  mitral  valve  they  were  in  scanty  numbers  and  the  growth 


THE  AETIOLOGY  OF  RHEUMATIC  FEVER       107 

was  not  a  vigorous  one.  No  detectable  clinical  result  followed 
the  inoculation  of  a  rabbit  in  the  usual  manner. 

The  last  case  (Case  8)  was  that  of  an  adult,  aged  32  years, 
who  came  to  St.  Mary's  Hospital  suffering  from  an  acute  "  sore 
throat."  The  throat  was  red  and  had  the  appearance  of  a 
rheumatic  angina.  There  were  muscular  pains  and  a  history 
of  a  previous  attack  of  rheumatic  fever.  The  heart  was 
extensively  diseased,  both  mitral  and  aortic  valves  were  in- 
competent, and  the  action  was  excited  and  the  precordial 
dullness  greatly  increased  in  extent.  The  condition  of  the 
heart  completely  bore  out  the  history  of  previous  rheumatism. 
A  culture  was  made  from  the  throat  in  the  milk  medium  and 
the  diplococcus  discovered  among  other  organisms.  This 
was  isolated  by  means  of  blood  agar  plates  and  a  pure  culture 
injected  intravenously  into  a  rabbit.  Three  days  after  inocu- 
lation there  was  dyspnoea  and  the  heart  was  acting  with 
great  rapidity.  Two  days  after  this  a  loud  mitral  murmur 
developed  and  the  respirations  were  now  extremely  rapid. 
The  rabbit  died  the  same  night  somewhat  unexpectedly. 
The  necropsy  showed  great  dilatation  of  the  heart  and  a 
large  vegetation  upon  the  mitral  valve  with  an  adherent  ante- 
mortem  blood-clot  filling  the  left  auricle.  We  demonstrated 
the  diplococci  in  the  granulation,  pericardium,  and  pleural 
exudation,  and  isolated  them  from  the  blood  and  cerebro-spinal 
fluid. 

It  will  be  seen  from  this  outline  that  on  four  different 
occasions  very  definite  results  have  been  obtained  with  rabbits. 
The  results  have  been  supported  by  demonstration  of  the 
diplococci  both  in  the  human  and  animal  tissues.  In  addition 
to  demonstrating  the  diplococci  in  the  tissues  in  most  of  these 
eight  cases  we  have  found  diplococci  in  the  heart  valves  or 
pericardium  in  eight  other  examples  of  undoubted  rheumatic 
fever,  and  in  the  pia  mater  and  brain  from  a  case  of  chorea  with 
extremely  violent  movements  which  proved  fatal  with  but  a 
slight  valvular  lesion  and  no  pericarditis. 

The  Outline  of  the  Methods  of  Bacteriological 
Investigation 

1.  The  material  for  examination.  The  materials  selected 
in  the  human  subject  for  bacteriological  examination  were  : 
(a)  the  pericardial  exudation  ;    (b)  the  blood  from  the  heart  ; 


ioS       THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

(c)  the  granulations  from  the  valves  ;  (d)  the  blood  from  the 
living  subject  during  an  attack  of  acute  rheumatic  pericarditis  ; 
and  (e)  the  exudation  from  the  inflamed  tonsils.  The  material 
in  the  fatal  cases  was  obtained  as  soon  as  possible  after  death 
and  the  necropsy  was  conducted  with  strict  precautions  for 
the  prevention  of  contamination,  all  the  instruments  being 
carefully  sterilised.  The  pericardium  was  exposed  very 
completely  by  removing  portions  of  the  ribs  as  well  as  the 
costal  cartilages  upon  the  left  side.  The  surface  was  seared 
with  hot  irons  and  any  fluid  present  was  drawn  up  in  sterilised 
pipettes.  The  point  of  the  pipette  was  broken  off  inside  the 
pericardial  cavity,  the  fluid  withdrawn,  and  the  pipette  at 
once  sealed.  The  surface  of  the  right  auricle  was  cauterised 
and  the  blood  withdrawn  in  a  similar  manner.  Finally,  a 
sterilised  suture  was  passed  through  the  cardiac  muscle  at  the 
apex  and  the  heart  pulled  over  to  expose  the  left  ventricle  ;  then 
the  posterior  surface  was  thoroughly  cauterised  and  rapidly 
opened  with  a  sterilised  knife,  the  walls  were  held  apart  by 
forceps,  the  blood-clot  was  removed,  and  the  mitral  valve  was 
exposed  and  curetted. 

2.  The  culture  media.  Both  liquid  and  solid  media  were 
used.  The  fluid  media  were  incubated  aerobically  and  anaero- 
bically.  The  temperature  of  incubation  was  370  C.  The 
following  media  were  used  :  {a)  Fluid.  (1)  Bouillon  and 
milk,  acidified  with  lactic  acid  ;  (2)  pork  broth  made  with 
Chapoteaut's  peptone  and  rendered  strongly  alkaline  (in 
imitation  of  Wassermann's  medium)  ;  (3)  bouillon  of  various 
degrees  of  acidity  and  alkalinity  ;  (4)  ascitic  fluid  ;  and 
(5)  cow's  milk  and  human  milk,  (b)  Solid  media.  Agar,  serum 
agar,  blood  agar,  glucose  agar,  glycerine  agar,  and  egg  albu- 
men. The  organism  grew  best  anaerobically  in  an  acid  medium. 
It  also  grew  aerobically  in  the  same  medium  and  in  blood 
smeared  upon  slightly  alkaline  agar.  The  anaerobic  cultures 
were  made  in  Pasteur's  pipettes,  which  were  exhausted  by 
an  air-pump  and  hermetically  sealed.  Films  were  invariably 
made  from  the  culture  used  for  experimental  purposes  before 
the  inoculation. 


THE  AETIOLOGY  OF  RHEUMATIC  FEVER       109 

Details  of  the  Clinical  Cases  and  Experiments 

The  following  is  a  detailed  account  of  the  eight  cases  of 
rheumatic  fever  with  the  investigations  made  from  them. 

Case  i.  A  girl  aged  17  years  was  admitted  into  St.  Mary's 
Hospital  on  January  16,  1899,  suffering  from  purpura  and 
rheumatic  morbus  cordis.  This  was  the  second  attack  of 
rheumatic  fever  and  in  addition  five  years  before  there  had 
been  an  attack  of  chorea.  This  case  was  published  in  detail 
in  the  Lancet  of  October  28,  1899,  p.  1163.  After  a  prolonged 
illness  the  patient  succumbed  to  severe  morbus  cordis.  A 
severe  attack  of  pericarditis  had  developed  while  in  the  hospital 
and  death  occurred  on  April  15.  At  the  necropsy,  which  was 
made  24  hours  after  death,  the  pericardium  was  found  to  be 
adherent,  the  adhesions  breaking  down  quite  easily.  The 
heart  was  enlarged  and  both  hypertrophied  and  dilated.  There 
was  mitral,  aortic,  and  tricuspid  valvulitis.  The  other  viscera 
showed  the  changes  usually  found  in  association- with  severe 
morbus  cordis.  There  was  one  small  infarct  in  the  spleen. 
Under  microsocopical  examination  the  cardiac  muscle  showed 
extreme  fatty  change.  Bacteriology.  With  Mr.  H.  G. 
Plimmer  upon  two  occasions  we  made  cultivations  from  the 
blood  of  the  patient  during  life,  taking  advantage  on  each 
occasion  of  a  venesection  that  had  been  done  for  right  heart- 
failure.  Both  times  we  obtained  from  the  tubes  of  the  milk 
medium  diplococci  arranged  in  chains.  The  medium  was 
treated  aerobically  and  anaerobically.  The  milk  tubes  were 
the  only  media  used. 

Note.  At  this  time  we  were  intent  upon  Achalme's  re- 
searches and  did  not  pursue  the  investigation  of  the  micro- 
cocci. In  one  of  the  anaerobic  tubes  we  found  a  bacillus  but 
were  unable  to  isolate  it,  and  after  considerable  investigation 
we  came  to  the  conclusion  that  it  was  a  contamination. 

Case  2.  A  patient,  aged  19  years,  was  admitted  into  St. 
Mary's  Hospital  on  December  4,  1899,  suffering  from  pains 
in  the  joints  and  morbus  cordis.  This  was  the  fourth  attack 
of  rheumatic  fever.  On  admission  there  was  advanced  cardiac 
disease.  Pericarditis  rapidly  developed  and  the  patient  died 
three  days  after  admission.  The  necropsy,  which  was  made 
14  hours  after  death,  showed  recent  pericarditis  with  turbid 
fluid  in  the  pericardial  sac,  moderate  stenosis  of  the  mitral  valve, 


no       THE  /ETIOLOGY  OF  RHEUMATIC  FEVER 

and  recent  vegetations  upon  the  aortic  valve.  Under  micro- 
scopical examination  the  cardiac  muscle  showed  much  fatty 
change.  Diplococci  were  demonstrated  in  the  granulations  of 
the  mitral  valve.  Bacteriology.  The  fluid  from  the  pericardium 
was  inoculated  into  the  medium  of  milk  acidified  with  lactic 
acid  and  aerobic  and  anaerobic  cultures  made.  At  this  time 
we  were  still  engaged  in  investigating  Achalme's  bacillus  and 
following  his  directions  the  anaerobic  tubes  were  left  for  10 
days.  In  both  the  aerobic  and  anaerobic  tubes  diplococci 
growing  in  a  streptococcal  arrangement  were  discovered. 
These  organisms  did  not  grow  upon  ordinary  agar  tubes. 
No  inoculations  were  made  into  animals. 

Note.  The  strepto-diplococci  were  not  thoroughly  investi- 
gated, but  it  was  found  that  an  ordinary  agar  medium  was 
not  suited  to  them. 

Case  3.  A  woman,  aged  20  years,  was  admitted  into  St. 
Mary's  Hospital,  moribund,  suffering  frOm  severe  rheumatic 
pericarditis  and  mitral  disease.  The  patient  died  the  same 
day.  The  investigation  was  incomplete.  Through  a  puncture 
in  the  pericardium  we  withdrew  some  sanious  pericardial  fluid 
in  a  sterilised  pipette.  Various  media  were  used  and  from 
a  bouillon  tube  and  the  milk  medium  we  obtained  diplococci 
contaminated  with  sarcinae. 

Note.  In  this  case  the  diplococci  grew  in  chains  in  the 
acid  milk  medium  in  a  manner  precisely  similar  to  that  noted 
in  the  two  preceding  cases.  Upon  ordinary  media  these 
organisms  failed  to  grow. 

Case  4.  A  patient,  aged  nine  years,  was  admitted  into  the 
Hospital  for  Sick  Children  Great  Ormond  Street,  on  October  n, 

1899,  suffering  from  dropsy  and  morbus  cordis.  There  was  no 
definite  history  of  rheumatism  and  no  history  of  scarlet  fever. 
Upon  admission  the  heart  was  found  to  be  enlarged  and  then- 
was  evidence  of  organic  mitral  disease.  There  were  dropsy, 
albuminuria,  and  ascites.  The  illness  was  prolonged  and  the 
condition  for  some  time  stationary,  but  in  March  active 
rheumatism  developed  and  nodules  appeared  ;  this  was 
rapidly  followed  by  cardiac  failure  and  death  on  March  20, 

1900.  At  the  necropsy,  which  was  held  36  hours  after  death, 
the  pericardium  was  found  to  contain  some  recent  plastic 
exudation  and  excess  of  clear  fluid.  The  valvular  disease  was 
slight  but  the  heart  was  much  dilated  and  hypertrophied.     The 


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THE  ETIOLOGY  OF  RHEUMATIC  FEVER       hi 

lungs  were  oedematous,  the  liver  was  "  nutmeg  "  in  appearance 
and  the  kidneys  and  spleen  were  firm.  Under  microscopical 
examination  the  cardiac  muscle  showed  granular  and  fatty 
changes  and  films  from  the  pericardial  fluid  and  heart  wall 
showed  diplococci.  Diplococci  were  also  found  in  the  mitral 
valve.  Bacteriology.  *(i)  Three  Pasteur  pipettes  of  the 
pericardial  fluid  were  incubated  aerobically  at  370  C.  for  three 
days  ;  and  (2)  blood-agar  tubes  were  inoculated  with  the 
pericardial  exudation  and  curetted  granulations  from  the 
mitral  and  aortic  valves.  The  diplococcus  was  found  in  every 
tube  in  pure  culture.  On  blood  agar  they  grew  in  discrete  and 
easily  detachable  colonies.  The  pericardial  fluid  had  increased 
in  opacity  and  flakiness.  The  reaction  of  the  pericardial  fluid 
was  distinctly  acid  and  there  was  no  offensive  odour.  Sub- 
cultures were  made  upon  the  milk  medium,  but  on  this  occasion 
they  did  not  grow  well.  Two  tubes  of  the  pericardial  fluid 
were  injected  intravenously  into  a- rabbit. 

Rabbit  No.  1.  Three  days  after  the  injection  the  animal 
was  wasting  and  the  left  shoulder-joint  was  swollen.  Nine 
days  afterwards  the  right  hip  and  shoulder  had  become  swollen. 
On  the  tenth  day  from  the  date  of  inoculation  the  rabbit  died 
from  broncho-pneumonia.  At  the  necropsy  the  heart  appeared 
enlarged,  but  there  was  no  definite  endocarditis  or  pericarditis 
visible.  There  was  a  definite  excess  of  clear  fluid  in  the 
pericardial  sac.  The  cartilages  of  the  affected  joints  were 
reddened  but  there  was  no  ulceration  of  their  surfaces.  The 
right  shoulder- joint  and  right  hip-joint  contained  an  excess 
of  clear  fluid.  The  left  shoulder- joint  contained  an  opaque 
fluid  and  films  afterwards  showed  that  the  fluid  contained  many 
endothelial  cells  from  proliferation  of  the  cells  lining  the 
synovial  membrance  of  the  joint  together  with  a  scanty  number 
of  leucocytes.  The  liver  was  dark  red  and  engorged  with 
blood.  The  spleen  was  firm  and  the  kidneys  were  apparently 
natural.  There  were  no  traces  of  abscess  formation  any- 
where. The  lungs  were  solid  in  patches  from  broncho- 
pneumonia. There  was  no  peritonitis.  Under  microscopical 
examination  the  strepto  -  diplococcus  was  demonstrated  in 
the  joint  fluid  and  the  mitral  valve  which  was  stained 
in  bulk.  The  heart  showed  no  fatty  change.  The  spleen  and 
kidneys  showed  nothing  distinctive.  Bacteriology.  The 
clear   fluid  from  the  right   shoulder    joint  and  heart   blood 


ii2       THE  /ETIOLOGY  OF  RHEUMATIC  FEVER 

were  used  for  inoculation  of  anaerobic  tubes  of  the  milk  medium 
and  48  hours  afterwards  these  tubes  were  found  to  contain 
the  organism  growing  vigorously  in  chains.  From  these 
tubes  six  blood  agar  cultures  were  made  aerobically.  The 
six  blood  agar  tubes  were  used  for  the  inoculation  of  the 
second  rabbit. 

Rabbit  No.  2.  Three  days  after  inoculation  the  right  knee 
joint  became  stiff  and  the  animal  had  lost  160  grammes  in 
weight  ;  four  days  afterwards  the  left  shoulder  became  swollen  ; 
five  days  afterwards  both  the  knee-joints  became  affected, 
and  the  right  was  more  swollen  ;  14  days  afterwards  the 
animal  was  much  wasted,  the  heart  was  rapid  and  feeble,  and 
the  animal  was  short  of  breath.  The  joints  still  remained 
swollen.  Seventeen  days  later  we  detected  a  basal  systolic 
murmur  over  the  position  of  the  large  vessels  ;  the  next  day 
this  became  fainter  and  then  disappeared.  With  this  dis- 
appearance the  heart  sounds  became  muffled  at  the  base  and 
we  diagnosed  as  the  most  probable  explanation  a  pericarditis 
with  effusion.  Twenty  days  after  inoculation  the  animal  died. 
The  swelling  of  all  the  joints  except  the  right  knee  had  gradually 
disappeared  some  days  before  death.  At  the  necropsy  the 
heart  was  enlarged  and  there  was  excess  of  clear  fluid  in  the 
pericardium  and  also  a  viscid  coagulum.  The  visceral  layer 
of  the  pericardium  showed  slight  roughening  over  the  base 
of  the  heart.  There  was  no  definite  endocarditis.  The  liver 
was  dark  red  and  mottled  with  white  spots  of  varying  size. 
The  spleen  was  firm.  The  kidneys  showed  no  definite  changes. 
There  was  no  trace  of  suppuration  in  any  of  the  viscera.  The 
affected  joints  were  reddened  and  except  in  the  case  of  the 
right  knee  contained  a  very  slight  excess  of  clear  fluid.  The 
right  knee  was  distended  with  an  opaque  fluid  which,  as  in  the 
case  of  the  first  rabbit,  contained  many  endothelial  cells  and 
also  mononuclear  and  polynuclear  leucocytes.  The  cartilages 
of  the  joints  were  unaffected.  The  tonsils  were  not  inflamed. 
There  was  no  peritonitis.  Under  microscopical  examination  : 
(1)  in  films  from  the  joint  the  diplococcus  was  demonstrated 
in  considerable  numbers  ;  (2)  the  heart  muscle  showed  definite 
fatty  change  in  many  fibres  ;  (3)  the  white  patches  in  the 
liver  proved  to  be  liver  cells  undergoing  necrosis  ;  (4)  the 
pericardial  fluid  clotted  rapidly  in  the  pipette  after  with- 
drawal,  the  clot  in  the   pericardial   sac  and  in  the   pipette 


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THE  ETIOLOGY  OF  RHEUMATIC  FEVER       113 

showing  a  delicate  fibrino-cellular  structure  ;  (5)  the  kidneys 
and  spleen  showed  no  change  of  note  ;  and  (6)  there  was  no 
peritonitis.  There  were  no  foci  of  suppuration  in  the  viscera. 
Bacteriology.  Cultures  were  made  from  the  heart  blood  and 
right  knee-joint  in  the  milk  medium  and  in  both  series  of  tubes 
the  diplococcus  was  found  growing  vigorously  in  pure  culture. 

Rabbit  No.  3.  A  third  rabbit  was  inoculated  with  the 
cultivations  upon  three  blood  agar  tubes  but  with  a  negative 
result . 

Rabbit  No.  4.  A  fourth  rabbit  was  inoculated  with  the 
contents  of  six  blood  agar  tubes  and  symptoms  once  more 
commenced  to  appear  on  the  third  da}'  and  developed  as 
follows.  On  the  third  day  after  inoculation  the  right  tarsal 
joint  became  swollen  and  tender.  On  the  sixth  day  after- 
wards there  was  wasting  and  the  left  knee-joint  was  swollen. 
On  the  seventh  da}-  afterwards  the  right  carpal  joint  swelled. 
The  heart  action  was  excited  and  we  suspected  a  mitral 
murmur.  The  next  day  this  murmur  was  definite  and  then 
became  less  audible.  On  the  tenth  day.  after  inoculation  we 
suspected  a  tricuspid  murmur  and  the  animal  was  killed  to 
verify  these  conclusions.  For  some  days  previously  there 
had  been  very  marked  dyspnoea.  At  the  necropsy  the  right 
carpal  and  tarsal  joints  were  distended  with  an  opaque  fluid  ; 
the  left  knee-joint  contained  clear  fluid.  The  cartilages  were 
reddened  but  otherwise  unaltered.  The  pericardium  con- 
tained an  excess  of  clear  fluid.  The  heart  was  dilated.  There 
was  no  visible  pericardial  roughening.  The  mitral  valve  showed 
definite  granulations,  the  appearance  exactly  resembling  an  early 
rheumatic  endocarditis.  The  tricuspid  valve  showed  a  still 
earlier  stage.  The  aortic  and  pulmonary  valves  were  un- 
affected. The  liver  was  dark  red  and  mottled  with  firm 
white  areas,  some  of  them  slightly  raised  above  the  surface. 
The  spleen  was  pale  but  firm.  The  kidneys  were  both  pale  and 
contained  a  few  white  areas,  firm  and  slightly  raised  above  the 
surface.  The  tonsils  were  unaffected.  In  none  of  the  \iscera 
were  there  any  foci  of  suppuration.  There  was  no  peritonitis. 
Under  microscopical  examination  (1)  in  the  parietal  layer  of  the 
pericardium  stretched  out  and  stained  in  bulk,  the  diplococci  were 
clearly  seen  in  great  numbers  along  the  course  of  the  vessels,  lying 
apparently  in  the  perivascular  lymphatic  spaces  ;  (2)  the  mitral 
valve  showed  on  section  an  early  granulation  on  the  auricular 

8 


ii4      THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 
surface,  consisting  of  a  proliferation  of  the  connective  tissue 
cells  of  that  part  of  the  valve.     The  delicate  endothelial  layer 
of  the  endocardium  passed  over  this  granulation,  and  in  the 
granulation  and  in  the  deeper  part  of  the  endocardium  diplococci 
were  visible.     They  could  be  seen  also  in  the  endocardium 
lining   the   auricle   and   ventricle   and   causing  in   places  cell 
proliferation.     They  were  also  present  in  considerable  number, 
in  the  retiform  tissue  at  the  base  of  the  valve,  that  is,  m  the 
position  of  the  valve  ring  ;   (3)  the  joint  fluid  showed  numerous 
diplococci  and  endothelial  cells,  also  eosinophiles  and  some 
polynuclear  leucocytes  ;    (4)  the  liver  showed  numerous  areas 
of  coagulation  necrosis  ;   (5)  the  kidneys  showed  areas  of  coagu- 
lation necrosis,   especially  in  the  region  of  the  convo  uted 
tubules  and  numerous  diplococci  in  these  areas  ;    (6)  the  heart 
muscle    showed    well-marked   fatty   and    other   degenerative 
changes  ;     and    (7)    there   was   no    peritonitis.     Bacteriology 
The  diplococci  were  obtained  in  pure  culture  from  the  joints  and 
heart  blood.     This  case  made  clear  several  important  facts  : 
(1)  the  earlv  and  definite  affection  of  the  heart  which  we  had 
suspected  previously  to  be  a  result  of  the  infection  became 
now  a  certainty;     (2)   the  post-mortem  appearances  of  the 
heart  and  the  microscopic  changes  were  analogous  to  those 
found  in  rheumatic  fever  ;    (3)  again  there  was  no  suppuration 
in  the  viscera  ;  and  (4)  the  kidneys  showed  that  the  diplococci 
were  present  in  great  numbers.     Inoculations  were  next  made 
from  the  cultivations  upon  six  blood  agar  tubes  obtained  from 
the  foregoing  case  and  were  injected  into  a  rabbit  in  the  usual 


wav. 


Rabbit  No  5.     The  rabbit  developed  the  following  symptoms. 
Four  days  after  the  inoculations  the  right  carpal  joint  was 
swollen  and  the  heart  was  rapid  and  excited.     Other  joint 
swellings  followed.     The  cardiac  rhythm  became  triple  and 
later  the  action  irregular.     There  were  marked  dyspnoea  and 
a  mitral  murmur.      Seven  days  after  we  heard  a  pericardial 
friction  sound  and  diagnosed  also  pneumonia  over  the  fronts 
of  both  lungs.     Upon  the  previous  day  a  great  quantity  of 
thick  white  urine  was  passed.     On  the  eighth  day  the  rabbit 
was  lalkd,  with  the  diagnosis  of  pericarditis,  valvulitis,  pneu- 
monia,  and   polyarthritis.     At   the    necropsy  the  appearance 
of  the  thoracic  organs  was  such  as  is   seen  in  severe  rheu- 
matic fever.     There  were  pleurisy  with  plastic  exudation  and 


■r 


FIG.  18 

Microphotograpli  showing  the  diplococcus  iu  the  mitral  valve  of 
rabbit.     \2100 


A 


FIG.  19 

Section  of  the  myocardium   of    a  rabbit  dead  from  experimental 

cardiae  dilatation,  stained  with  osniic  acid  to  show  the  fatty  changes 

in  the  muscular  fibres  (A). 


THE  ETIOLOGY  OF  RHEUMATIC  FEVER      115 

pneumonia  over  those  parts  of  the  lung  that  covered  the  heart. 
There  were  also  mediastinitis  and  recent  plastic  pericarditis 
with  some  effusion  of  clear  fluid  in  the  pericardial  sac.     The 
heart   was   greatly   dilated   and   the   muscle   was   pale.     The 
mitral  valve  showed  early  endocarditis.     The  liver  was  en- 
larged and  mottled  red  and  white,  just  such  an  appearance 
as  is  seen  in  acute  rheumatism.     There  were  no  white  firm  areas 
as  in  former  cases.     The  spleen  was  enlarged  and  was  softer 
than- in  previous  cases.     Both  kidneys  were  pale.     The  joints 
contained  an  opalescent  fluid  and  the  connective  tissue  around 
them  had  the  gelatinous  appearance  suggestive  of  a  nodule 
formation.     The  tendon  sheaths  around  the  right  tarsal  joints 
contained  an  opaque  fluid.     There  was  no  peritonitis.     The 
tonsils  were  not  affected.     The  bladder  was  much  distended 
and  thick  white  urine  was  withdrawn  by  a   pipette.     This 
fluid  on  adding  acetic  acid  cleared  rapidly.     The  urine  under 
the  microscope  showed  numerous  dumb-bell  shaped  crystals 
of  uric  acid,  diplococci,  and  granular  casts.     There  was  no 
suppuration  in  the  viscera.     The  heart  muscle  was  at  once 
teased  and  examined  microscopically.    Numerous  clear  granule  s 
were  seen  in  the  fibres,  which  stained  faintly  with  osmic  acid. 
Under  microscopical  examination  the  diplococci  were  demon- 
strated in  the  mitral  and  tricuspid  valves  and  in  the  peri- 
cardium ;    also  in  the   joints,  connective  tissue  around  the 
joints,  kidneys,  and  liver.     In  the  lungs  and  pleurae  they  were 
present  in  very  great  numbers,  especially  towards  the  surface. 
Bacteriology.     The  inoculations  were  made  in  the  usual  way 
and  a  free  growth  obtained  upon  blood  agar.     The  organisms 
were  in  this  case  isolated  from  the  bladder. 

Note.  This  case  presented  the  most  striking  resemblance 
to  severe  rheumatic  fever  both  clinically  and  in  the  patho- 
logical results.  The  condition  of  the  thoracic  viscera  was 
just  as  is  seen  in  the  virulent  pleuro-pericarditis  of  rheumatic 
fever  in  childhood.  The  diplococci  in  this  case  were  demon- 
strated in  the  lungs  and  liver. 

Case  5.  A  youth,  aged  16  years,  was  admitted  into  St. 
Mary's  Hospital  on  March  20,  1900,  suffering  from  rheumatic 
pericarditis.  This  was  the  second  attack  of  rheumatic  fever 
and  in  addition  he  had  suffered  from  chorea  at  the  age  of  15 
years.  The  illness  had  commenced  a  fortnight  previously 
to  admission  with  a  sore  throat  and  pain  in  the  right  knee, 


n6      THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

followed  by  shivering,  and  pain  in  the  chest.  On  admission 
there  was  general  pericardial  friction  and  mitral  (and  a  suspicion 
of  aortic)  endocarditis.  The  heart  was  much  dilated  and  right 
heart  failure  was  threatened.  On  this  account  he  was  vene- 
sected. This  patient  made  an  excellent  recovery  from  the 
pericarditis,  but  left  the  hospital  in  May  with  evidence  of 
organic  valvular  disease.  Bacteriology.  On  March  24,  the 
patient  was  venesected  and  due  precautions  were  taken  to 
obtain  the  blood  free  from  contamination.  Three  different 
media  were  used  :  (1)  the  milk  medium  (acid)  ;  (2)  the  pork 
medium  (strongly  alkaline)  ;  and  (3)  the  bouillon  medium 
(alkaline).  Anaerobic  tubes  were  made  of  these  media.  In 
one  anaerobic  milk  tube  the  strepto-diplococci  were  growing 
vigorously.  The  remaining  tubes  were  sterile.  From  the 
anaerobic  milk  tube  sub-cultures  were  made  and  a  blood 
agar  tube  was  inoculated  upon  which  discrete  colonics  of  the 
diplococci  made  their  appearance.  Sub-cultures  were  made 
and  the  remainder  injected  intravenously  into  a  rabbit. 

Rabbit  No.  6.  Four  days  after  inoculation  the  rabbit  limped, 
the  right  knee-joint  was  swollen,  and  it  had  lost  flesh.  Eleven 
days  afterwards  it  was  still  limping  and  was  thinner.  Twenty- 
one  days  afterwards,  though  the  heart  was  very  rapid,  the 
limp  had  disappeared  and  a  slight  improvement  set  in.  Five 
weeks  afterwards  there  was  a  relapse  and  both  hind  legs 
became  affected,  and  the  animal  could  not  support  the  weight 
upon  them.  It  was  now  very  thin.  The  heart  sounds  were 
very  feeble  and  rapid  but  there  was  no  murmur.  This  affec- 
tion of  the  hind  limbs  seemed  to  be  a  paralytic  phenomenon 
and  no  swelling  of  the  joints  was  apparent.  There  was  no 
twitching.  This  symptom  also  passed  away  in  about  three 
weeks  and  the  animal  could  use  both  hind  legs  again  in  a 
normal  manner. 

Case  6.  A  girl,  aged  thirteen  and  a  half  years,  was  admitted 
nto  St.  Mary's  Hospital  on  March  25,  1900,  suffering  from 
active  rheumatism  and  morbus  cordis.  In  January  1900, 
the  first  attack  of  rheumatism  occurred.  The  present  illness 
had  lasted  three  weeks.  On  admission  the  child  was  very  ill. 
There  were  numerous  nodules,  the  heart  was  dilated,  there  was 
organic  mitral  disease,  and  there  was  general  pericarditis.  She 
grew  rapidly  worse  and  died  on  the  30th.  The  necropsy, 
which  was  made  eight  hours  alter  death,  showed  recent  lymph 


THE  .ETIOLOGY  OF  RHEUMATIC  FEVER       117 

upon  the  visceral  pericardium  and  turbid  fluid  in  the  sac.  There 
were  recent  granulations  upon  the  mitral  valve  and  some 
thickening  of  the  cusps  of  the  aortic  valve.  The  liver  showed 
an  early  nutmeg  change.  The  spleen  was  firm  and  dark.  The 
kidneys  were  pale.  The  pericardial  fluid  was  definitely  acid 
in  reaction.  On  microscopical  examination  the  heart  showed 
very  marked  fatty  change  in  the  muscle  fibres  and  diplococci 
were  demonstrated  in  the  granulations  of  the  mitral  valve. 
Bacteriology.  Films  made  of  the  pericardial  fluid  after 
incubation  showed  diplococci  and  a  short  bacillus.  A  cusp 
of  an  aortic  valve  and  a  piece  of  the  mitral  valve  were  stained 
and  examined  in  bulk  but  no  organisms  were  found.  A  section 
of  the  mitral  valve  showed  the  cocci  in  the  granulations.  The 
following  cultures  were  made  :  (a)  the  pericardial  fluid  was 
incubated  in  pipettes  ;  (b)  the  lymph  was  introduced  into 
(1)  blood  agar,  (2)  the  milk  medium  (acid),  and  (3)  the  pork 
medium  (alkaline)  ;  and  (c)  fragments  curetted  from  the 
mitral  granulations  Were  also  placed  in  the  same  media.  The 
heart  blood  was  also  introduced  into  other  tubes  of  the  same 
media.  Anaerobic  tubes  were  made  of  the  milk  medium 
(acid).  The  results  were  as  follows.  Two  of  the  pipettes  of 
pericardial  fluid  were  sterile,  one  contained  the  diplococci,  but 
with  them  numerous  small  bacilli,  and  the  odour  of  the  fluid 
was  offensive.  The  blood  agar  was  sterile.  The  tube  of  the 
heart  blood  was  sterile.  A  blood  agar  tube  was  made  from 
the  pericardial  fluid.  The  following  inoculations  into  animals 
were  made,  1.  Five  minims  of  the  pericardial  fluid  con- 
taining the  diplococci  and  bacilli  were  injected  intravenously 
but  the  result  was  negative.  2.  Later  the  contents  of  six 
blood  agar  tubes  from  a  sub-culture  were  inoculated  but  the 
result  was  again  negative.  Later  a  third  attempt  was  made. 
The  culture  upon  blood  agar  was  growing,  but  not  vigorously, 
and  a  sub-culture  was  accordingly  made  in  the  acid  medium 
and  then  this  re -transferred  to  six  blood  agar  tubes. 

Rabbit  No.  7.  A  rabbit  was  inoculated  but  no  apparent 
result*  followed  until  three  weeks  after  the  inoculation,  when 
a  definite  systolic  murmur  was  detected  at  the  apex  and  the 
temperature  in  the  rectum  was  found  to  be  102. 8°  F.  No 
joint  lesion  developed  and  after  detecting  the  murmur  each 
day  for  a  week  the  animal  was  killed.  The  necropsy  showed 
definite  tricuspid  and  mitral  endocarditis  and  a  definite  excess 


nS      THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

of  clear  fluid  in  the  peritoneal  cavity.  The  organism  was 
demonstrated  in  the  valves  and  parietal  pericardium  in  which 
there  was  definite  cellular  exudation. 

Note.  This  case  corresponded  clinically  to  the  well-known 
rheumatic  condition  of  organic  valvular  disease  occurring 
without  arthritis. 

The  pyrexia  in  the  rabbits  in  these  cases  was  moderate, 
the  range  being  from  ioi°  to  103. 40  F.  The  temperature 
was  taken  in  the  rectum.  In  the  more  severe  cases  the  fever 
was  continuous  though  with  some  oscillation. 

Case  7.  A  boy,  aged  nine  years,  was  admitted  into  the 
Hospital  for  Sick  Children,  Great  Ormond  Street,  on  February 
26,  1900,  suffering  from  rheumatic  fever  from  which  his  mother 
also  had  suffered.  On  admission  there  were  pericarditis  and 
arthritis.  The  illness  was  prolonged  and  after  a  partial  im- 
provement a  relapse  of  carditis  occurred  and  terminated 
fatally  on  April  30.  At  the  necropsy,  which  was  made  30 
hours  after  death,  the  tonsils  were  found  to  be  large  and 
inflamed.  There  was  consolidation  of  areas  of  both  lungs. 
The  heart  was  large  and  the  muscle  pale  and  soft.  The  peri- 
cardium was  generally  adherent,  the  adhesions  breaking  down 
easily.  There  were  recent  granulations  upon  the  mitral  and 
aortic  valves  and  the  pulmonary  valve  showed  very  earl)7 
inflammation.  The  liver,  kidneys  and  spleen  showed  the 
usual  changes.  At  the  microscopical  examination  the  im- 
portant fact  was  the  demonstration  of  the  diplococci  in  the  tissue 
of  a  rheumatic  nodule.  The  nodule  was  of  about  the  size  of  a 
small  pea  and  was  situated  over  the  left  olecranon.  The 
diplococci  were  in  small  clumps  in  the  fibrous  tissue.  We  are 
not  aware  that  they  have  been  demonstrated  before  in  these 
structures,  which  are  looked  upon  as  extremely  characteristic 
of  rheumatic  fever.  Bacteriology.  The  recent  granulations 
on  the  mitral  and  aortic  valves  were  curetted  and  the  heart 
blood  taken  in  a  sterilised  pipette.  Films  from  the  mitral 
granulations  showed  a  few  diplococci.  The  milk  medium 
and  blood  agar  tubes  were  used.  The  milk  medium  was  treated 
anaerobically,  and  from  the  curetted  granulations  of  the 
mitral  valve  a  growth  of  strepto-diplococcus  was  obtained 
but  it  was  not  abundant.  The  usual  blood  agar  tubes  were 
made  but  the  growth  was  poor.  Intravenous  inoculation  in 
a  rabbit  (No.  8)  proved  negative. 


THE  .ETIOLOGY  OF  RHEUMATIC  FEVER       119 

Case  8.  A  man,  aged  28  years,  came  into  St.  Mary's 
Hospital  on  June  7,  1900,  suffering  from  a  "  sore  throat."  The 
illness  had  commenced  with  general  malaise  and  pains  in  the 
limbs  and  joints.  There  was  a  history  of  a  definite  attack  of 
rheumatic  fever  four  years  before.  The  throat  was  injected 
and  the  tonsils  were  in  a  condition  of  acute  catarrh.  The  heart 
was  much  enlarged  and  both  mitral  and  aortic  valves  were 
incompetent.  The  enlargement  of  the  heart,  the  character 
of  the  murmurs,  and  the  pulse  all  pointed  to  a  previous  attack 
of  rheumatic  carditis  and  confirmed  the  history  of  previous 
rheumatism.  We  diagnosed  from  the  history,  the  appearance 
of  the  throat,  and  the  excited  action  of  the  heart  that  the 
condition  was  one  of  rheumatic  tonsillitis.  A  culture  was  made 
upon  the  acid  milk  medium  and  the  tube  incubated  aerobically. 
Minute  diplococci  were  found  in  a  film  in  association  with 
other  micro-organisms.  Bacteriology.  Twenty-four  hours 
after  the  culture  had  been  made  a  film  showed  that  a  diplo- 
coccus  was  growing  in  association  with  other  micro-organisms 
and  blood  agar  tubes  were  inoculated  from  the  milk  culture. 
On  the  1 2th  blood  agar  plates  were  made  from  these  tubes  and 
a  diplococcus  isolated  and  transferred  to  blood  agar  tubes.  The 
diplococcus  resembled  morphologically  and  in  its  growth  that 
found  in  the  seven  preceding  cases.  On  the  14th  the  contents 
of  six  blood  agar  tubes  were  injected  intravenously  into  a  rabbit. 

Rabbit  No.  9.  On  June  15,  the  respirations  were  rapid 
and  the  action  of  the  heart  was  excited.  On  June  16,  the 
heart  sounds  were  loud  and  the  action  was  very  rapid.  On 
June  18,  there  was  suspicion  of  a  systolic  apical  murmur 
and  of  pleurisy.  On  June  19,  a  very  loud  systolic  apical 
murmur  was  discovered  and  both  pleurisy  and  pericarditis 
were  suspected.  The  rabbit  died  in  the  night  somewhat 
unexpectedly.  At  the  necropsy  the  heart  was  found  to  be 
greatly  dilated  and  there  was  some,  excess  of  fluid  in  the 
pericardial  sac.  The  mitral  valve  showed  a  large  vegetation 
upon  the  anterior  flap  and  to  this  a  large  ante-mortem  clot 
occupying  much  of  the  left  auricle  was  firmly  adherent.  The 
posterior  flap  was  reddened.  The  aortic  valves  were  reddened 
and  the  aorta  close  to  the  valve  showed  a  small  patch  of  aortitis. 
The  tricuspid  valve  was  reddened.  The  pulmonary  valve 
was  apparently  normal.  There  was  recent  fibrinous  exudation 
in  the  pleurae.     The  lungs  were  engorged  and  solid  in  small 


120       THE  /ETIOLOGY  OE  RHEUMATIC  FEVER 

,  close  beneath  the  pleurae.  There  was  no  trace  of 
suppuration  in  any  of  the  viscera.  Under  microscopical 
examination  the  diplococci  were  demonstrated  in  the  vegeta- 
tion of  the  mitral  valve,  in  the  pericardium,  and  pleural  exuda- 
tion. Bacteriology.  Cultivations  were  made  ancrobically 
in  the  acid  medium  from  (a)  the  blood  and  (6)  the  cerebro- 
spinal fluid  from  the  lateral  ventricles.  In  both  instances  the 
diplococci  were  obtained  in  pure  culture. 

Note.  This  case  by  the  light  of  the  former  one  is  of  extreme 
interest.  I.  It  demonstrated  conclusively  that  these  diplococci 
when  present  in  the  throat  of  a  man  the  subject  of  rheumatic 
fever  will,  if  isolated  during  an  attack  of  angina  faucium, 
cause  non-suppurative  valvulitis  and  pericarditis,  when 
inoculated  intravenously  into  a  rabbit.  2.  The  presence  of 
the  micro-organism  in  the  cerebro-spinal  fluid  is  very  suggestive 
when  the  close  association  of  chorea  and  rheumatic  fever  is 
considered  from  this  point  of  view. 

General  Conclusions  and  Remarks 

Concerning  the  isolation  of  the  diplococci.  I.  We  have 
demonstrated  these  diplococci  in  eight  successive  cases  of 
acute  rheumatism.  2.  They  have  been  present  in  five  cases 
in  pure  culture.  3.  We  have  obtained  them  (a)  from  the  blood 
of  living  patients  suffering  from  acute  rheumatic  pericarditis  ; 
(b)  from  the  pericardial  fluid  and  from  the  fragments  of  granu- 
lations removed  from  the  valves  after  death  ;  and  (c)  from 
the  throat  of  the  living  patient  suffering  from  rheumatic 
tonsillitis.  4.  We  have  isolated  them  and  grown  them  in  an 
acid  medium  and  also  upon  blood  agar.  5.  They  have  also 
grown  in  the  pericardial  fluid,  which  we  proved  on  those 
occasions  to  be  acid.  6.  They  do  not  thrive  on  ordinary 
media.  7.  We  have  isolated  them  in  pure  culture  from  the 
joint  exudation,  heart  blood,  urine  from  the  bladder,  and 
cerebro-spinal  fluid  of  rabbits  that  had  been  inoculated  with 
a  sufficient  dosage. 

Concerning  the  demonstration  of  the  diplococci  in  the  tissues. 
i.  We  have  demonstrated  them  in  the  cardiac  valves,  peri- 
cardium, and  tonsils,  and  in  a  nodule  in  fatal  cases  of  rheu- 
matism. 2.  We  have  demonstrated  them  in  the  cardiac  valves, 
pericardium,     joint     exudation,     kidneys,     liver,     connective 


\  /'     ••■-•' 


FIG.   20 

Film    showing   the  diplococcus  in  chain   form  in    the    incubated 

pericardial   exudation    from   a   case   of  fatal   pericarditis.     (Zeiss, 

obi.  T\,  oc.  3.) 


W      -.'■    ..'' 


S* 


• 

&~- 

■■";?% 

f 

.-.  ■'  -'; 

/■  "$L.    :',  '■' 

'  '     <''■*■■  , 

FIG.  21 

Film  showing  the  Diplococcus  rheumaticus  growing  in  the  acid-milk  medium. 
(Zeiss,  obj.  A,  oc.  4.) 


THE  /ETIOLOGY  OF  RHEUMATIC  FEVER       121 

tissues,  pleurae,  cerebrospinal  fluid,  lungs,  and  urine  of  rabbits 
inoculated  intravenously. 

Concerning  the  results  produced  by  inoculation  of  these  organisms 
intravenously  into  rabbits.  1.  They  produce  a  polyarthritis, 
bursitis,  and  tenosynovitis.  2.  This  polyarthritis  may  com- 
pletely disappear.  3.  In  some  of  the  joints  that  have  been 
affected  for  a  considerable  time  the  fluid  is  opaque  and  contains 
fibrin,  endothelial  cells,  mononuclear  and  polynuclear  leucocytes . 
In  other  joints  the  exudation  is  clear.  4.  In  one  case  the}' 
produced  a  paresis  of  the  lower  extremities  which  passed  off 
in  about  three  weeks.  5.  They  produce  multiple  valvulitis 
and  pericarditis,  both  non-suppurative.  6.  They  produce 
in  the  liver  and  kidneys  a  condition  of  coagulation  necrosis. 
This  in  the  case  of  the  kidneys  chiefly  occurs  in  the  convoluted 
tubules.  7.  They  produce  plastic  pleurisy  and  pneumonia. 
8.  The  urine  is  acid  and  loaded  with  urates.  9.  They  have  not 
produced  suppurative  foci  in  the  viscera.  10.  They  produce 
in  the  myocardium  a  condition  of  fatty  degeneration  and 
destruction  of  the  muscle  fibres  analogous  to  that  found  in  the 
human  heart  as  a  result  of  severe  rheumatic  carditis.  11.  The 
clinical  symptoms  are  characterised  by  multiple  painful  joint 
swellings,  wasting,  with  (in  the  less  severe  cases)  a  maintenance 
of  the  appetite.  There  is  moderate  pyrexia.  12.  The  heart 
is  affected  early  ;  tachycardia,  dyspnoea,  and  irregularity  of 
cardiac  action,  together  with  valvular  murmurs,  pericardial 
and  pleural  friction,  have  all  been  observed.  13.  The  clinical 
symptoms  are,  on  the  whole,  remarkably  constant  when  the 
organism  is  passed  from  animal  to  animal,  though  the  ten- 
dency is  for  increase  in  the  severity  of  the  cardiac  lesions  and 
diminution  in  the  arthritis. 

I.    The  Morphology  and  other  Characteristics  of 

THE    DlPLOCOCCUS 

We  are  not  as  yet  in  a  position  to  state  fully  the  morpho- 
logical characteristics  of  this  micro-organism.  Our  research 
has  been  concerned  more  especially  with  the  elucidation  of  the 
symptoms  and  morbid  changes  that  are  the  result  of  their 
access  to  the  living  body.  We  have,  however,  ascertained  the 
following  details. 

1.  They  are  micrococci  associated  in  pairs,  the  individual 


122       THE  ETIOLOGY  OF  RHEUMATIC  FEVER 

elements  of  which  vary  somewhat  in  sizj  but  average  0.5  M  in 
diameter,  as  measured  by  Zeiss's  micrometer  eyepiece. 

2.  In  liquid  media  the}7  grow  in  chains  of  varying  length.  In 
solid  media  the  y  grow  in  masses  that  resemble  the  arrangement 
of  staphylococci. 

3.  They  grow  both  acrobically  and  anaerobically.  They 
may  be  culivated  upon  ordinary  media  but  do  not  thrive  and 
rapidly  lose  both  their  virulence  and  characteristic  appearances. 
When  isolating  them  from  the  tissues  we  have  succeeded  best 
with  a  medium  of  milk  and  bouillon  slightly  acidified  with 
lactic  acid,  and,  on  the  whole,  the  anaerobic  tubes  have  proved 
more  suitable  to  them  than  the  aerobic.  When  they  have  been 
isolated  they  grow  well  upon  blood  agar  acrobically  at  a 
temperature  of  3J0  C,  at  which  temperature  the  milk  tubes 
w.re  also  incubated.  Upon  blood  agar  they  form  in  24  hours 
small,  raised,  yellowish- white,  discrete  colonies,  the  average 
size  of  which  is  0.456  millimetre.  The  colonies  are  more  or 
less  circular  and  have,  under  a  high  magnification,  a  slightly 
granular  appearance.  By  transmitted  light  they  show  a  darker 
centre. 

4.  They  stain  with  the  various  aniline  dyes,  though  by 
Gram's  method  they  are  easily  decolourised.28  The  stain 
which  we  have  used  for  them  in  the  tissues  and  which  has 
given  the  best  result  has  been  carbol-thionin.  The  meta- 
chromatism  that  is  produced  with  this  stain  has  assisted  us 
in  differentiating  them  from  the  tissues  in  which  they  were 
lying,  for  when  deeply  stained  they  appear  a  deep  blue,  whereas 
the  tissues  are  usually  a  light  blue  or  have  a  red  tinge. 

II.    The  Relation  of  these  Diplococci  to  those 
Isolated  by  other  Observers 

There  can,  we  think,  be  but  little  doubt  that  these  diplococci 
are  identical  with  those  discovered  by  Triboulet  in  1897  and 
by  Wassermann  in  1899.  Triboulet  isolated  them  from  the 
blood  in  acute  rheumatism  and  grew  them  anaerobically.  He 
also  produced  in  one  instance  a  valvular  lesion  in  a  rabbit  but 
did  not  produce  polyarthritis.  In  spite  of  this  absence  of 
joint  lesions  he  thought  these  diplococci  were  the  cause  of 
rheumatism.  Wassermann  originally  isolated  them  after 
death  from  a  case  of  rheumatism  and  produced  polyarthritis 
and  tenosynovitis  in  a  series  of  rabbits.     He  grew  them  best 


THE  AETIOLOGY  OF  RHEUMATIC  FEVER       123 

on  a  strongly  alkaline  medium  aerobically,  but  did  not 
apparently  obtain  any  valvular  lesions.  In  addition  to  the 
isolated  lesion  obtained  by  these  observers  the  entire  picture 
of  rheumatic  fever  resulted  in  our  cases.  We  have  succeeded 
with  acid  but  failed  with  strongly  alkaline  media. 

III.    Is  this  Organism  the  Cause  of  Rheumatic  fever  ? 

In  the  face  of  the  statements  by  Achalme,  Thiroloix,  Betten- 
court,  Litten,  and  others,  we  cannot  claim  that  this  diplococcus 
is  the  only  cause  of  rheumatic  fever.  More  extended  observa- 
tions will  doubtless  settle  this  most  important  point.  That 
it  is  one  cause  we  believe  to  be  proved  to  all  practical  purposes 
by  this  investigation,  and  we  believe  it  highly  probable  that  it 
will  prove  to  be  the  cause  of  all  cases  of  rheumatic  fever  which 
conform  to  the  usual  type  of  the  disease,  for  the  disease  in 
man,  as  we  have  insisted  before,  is  a  viry  definite  one  and 
therefore  probably  caused  by  a  specific  micro-organism. 

IV.    The  Clinical  Likeness  between  Rheumatic 
Fever  and  the  Disease  Produced  by  the     . 
Diplococcus  in  Rabbits 

The  resemblance  between  the  disease  produced  in  rabbits 
and  the  rheumatic  fever  of  man  is,  we  think,  a  very  striking 
one.  There  is  moderate  pyrexia  and  wasting,  and  the  occur- 
rence of  a  painful  polyarthritis,  which  is  metastatic  and  may 
entirely  disappear.  The  tissues  around  the  joints,  such  as 
the  tendons  and  bursae,  are  also  affected,  and  the  large  joints 
are  especially  liable  to  this  arthritis.  The  heart  is  affected 
early,  even  before  the  joints  or  *  irrespectively  of  the  joint 
affection.  In  the  severe  cases  there  occur  pericarditis,  endo- 
carditis, pleurisy,  and  pneumonia,  and  the  myocardium  suffers 
as  it  does  in  acute  rheumatism.  The  urine  is  acid  and  loaded 
with  urates.  There  is  no  suppuration  in  the  viscera  and 
the  peritoneum  as  a  rule  escapes  as  it  does  in  rheumatism.  In 
one  carse  following  the  arthritis  there  occurred  a  passing  weak- 
ness of  the  hind  limbs.  We  do  not  venture  to  explain  this, 
but  think  it  suggestive  of  paralytic  chorea. 

The  course  of  the  disease  is,  as  in  rheumatic  fever,  prolonged 
and  inclined  to  recovery  unless  the  dose  is  a  large  one.  Finally 
there  is  a  tendency  to  exacerbations  of  symptoms  similar  to 


i24      THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

those  so  frequently  observed  in  the  rheumatism  of  childhood. 
In  this  it  is  well  known  that  even  when  progress  seems  to  be 
satisfactory  there  may  be,  without  assignable  cause,  a  sudden 
exacerbation  of  symptoms  which  may  almost  as  quickly 
disappear;   in  the  rabbit  also  these  variations  maybe  noticed. 

V.     The  Demonstration  of  the  Diplococcus  in  the 

Tissues 

The  demonstration  of  these  organisms  in  the  human  tissues 
is  not  easy.  We  think  that  one  reason  for  the  difficulty  lies  in 
tli«'  fact  that  rheumatic  fever  is  essentially  a  disease  to  which 
there  is  great  resistance.  Even  in  fatal  cases  the  repara- 
tive processes  arc  often  well  advanced  at  the  site  of  some  of 
the  local  lesions.  Such  tissues,  too,  as  the  granulations  upon 
valves,  the  nodules,  and  the  pericardial  exudation  are  among 
the  more  difficult  of  the  structures  that  require  investigation 
under  the  highest  powers  of  the  microscope.  The  micro- 
organism, again,  is  a  very  minute  one  and  often  present  in 
compact  masses  which  arc  liable  to  be  mistaken  for  Mast- 
zi  lien.  Their  discovery  in  the  rabbit  is  far  easier,  for  the 
animal  can  be  killed  early  in  the  disease,  and  it  is  a  point  of 
great  interest  that  numerous  diplococci  can  be  demonstrated 
in  the  pericardium  before  any  cellular  reaction  of  consequence 
has  had  time  to  develop.  The  tissues  have  afforded  us  the 
very  greatest  assistance  both  in  localising  the  diplococcus 
and  in  getting  a  true  picture  of  its  appearance  in  the  viscera. 

We  are  not  at  present  in  a  position  to  state  with  confidence 
the  number  of  diplococci  that  are  present  in  the  human  tissues, 
but  have  good  reason  to  believe  that  at  some  period  of  the 
illness  they  are  present  in  large  numbers.  Usually  they  are 
seen  in  small  clumps,  but  when  they  reach  a  free  surface 
they  are  sometimes  in  large  masses,  although  the  individual 
diplococcus  is  very  small.  In  the  short  description  that  is 
given  below  of  their  occurrence  in  particular  regions,  such  state- 
ments as  are  made  are  supported  by  the  proof  of  microscopic 
demonstration. 

i.  Occurrence  in  the  heart.  The  valves  of  the  heart  arc 
attacked  from  within  and  the  diplococci  are  not  at  first  found 
upon  the  surface.  In  both  man  and  rabbits  we  have  examined 
valves  in  a  very  early  stage1  of  the  local  disease  and  found  the 
diplococci  beneath  the  endocardium  in  the  substance  of  the 


•::■ 


••' 


O 


az> 


A       . 


fk;.  22 

Section  of    rheumatic   nodule    showing    diplococci    in    the    tissue. 
(Zeiss,  obj.  ,'..,  oc  3).     A.  A.  diplococcus. 


j 

".% 

- 

... 

//? 

•"       y*.  ••  • 

A*- 

••I 

FIG.  23 

Section  of  a  subcutaneous  nodule  in  a  rabbit  produced   by  intra- 
venous inoculation  of  the  diplococcus.  Many  of  the  organisms  are 

seen  in  the  swollen  tissues.  (Zeiss,  oj.  ,'.,,  OC.  3). 


THE  ETIOLOGY  OF  RHEUMATIC  FEVER      125 

valve  and  at  the  base  in  the  region  of  the  valve  ring.  When 
the  connective-tissue  proliferation  they  produce  in  the  valve 
becomes  a  granulation  and  breaks  down  then  they  may  be 
found  on  the  surface  ;  they  may  also  be  found  in  the  connective- 
tissue  cells  of  the  valve  and  chorda?  tendineae.  It  is  especially 
difficult  in  our  experience  to  demonstrate  them  in  the  necrotic 
material  of  an  early  granulation.  They  are  found  in  man  in 
the  deeper  part  of  the  visceral  pericardium,  in  the  fibrino- 
cellular  exudation,  and  in  the  parietal  pericardium.  In  the 
rabbit  they  can  be  seen  in  the  visceral  pericardium  and  in  the 
parietal  pericardium  following  the  course  of  the  blood-vessels. 
In  the  heart-wall  they  are  seen  sometimes  in  the  areolar 
tissue  near  the  blood-vessels  in  the  intermuscular  septa.  In 
the  very  earliest  stages  these  organisms  can  be  discovered  in 
these  tissues  without  having  apparently  caused  any  reaction, 
but  a  proliferation  of  connective-tissue  cells  and  a  free  exudation 
of  leucocytes  is  usually  easily  recognised  as  a  result  of  their 
presence.  During  the  actue  phase  of  rheumatic  pericarditis 
they  circulate  in  the  general  blood-stream. 

2.  Occurrence  in  the  nodule.  The  discovery  of  the  diplococci 
in  the- rheumatic  nodule  is,  we  think,  of  especial  interest,  for 
this  lesion  above  all  is  looked  upon  as  highly  characteristic  of 
rheumatic  fever.  It  is  a  strong  point  in  favour  of  the  view 
that  these  diplococci  are  the  cause  of  the  symptoms  of  rheumatic 
fever.  Further,  it  completes  the  proof  of  the  analogy  of  this 
lesion  with  the  valvular  and  pericardial  inflammation — an 
analogy  which  has  been  long  suspected  by  clinicians.  In  the 
rabbit  the  connective  tissues  near  the  affected  joints  are  some- 
times swollen  and  gelatinous.  In  one  case  a  nodule  appeared 
over  a  vertebral  spine  and  after  a  month  gradually  disappeared. 
Sections  of  the  tissue  in  this  condition  show  the  three  zones  that 
are  found  in  the  rheumatic  nodule.  This  series  of  changes  in 
these  tissues  is  a  strong  support  of  the  views  expressed  by 
Dr.  Poynton  and  Dr.  Still  in  the  Transactions  of  the  Patho- 
logical Society  of  London  for  1899  upon  the  Structure  of  the 
Rheumatic  Nodule. 

3.  Occurrence  in  the  kidney.  This  we  believe  to  be  one  of 
the  most  interesting  aspects  of  the  subject  and  wea  briefly 
recapitulate  here  the  chief  facts  that  have  come  to  light. 
In  this  first  place,  there  is  the  definite  proof  of  their  occurrence 
in  the  kidneys  of  rabbits  after  death.    They  are  found  especially 


126      THE  .ETIOLOGY  OF  RHEUMATIC  FEVER 

in  the  convoluted  tubules  lying  in  the  cells  and  produce  coagu- 
lation necrosis  of  the  protoplasm.     Secondly,  their  presence 
is  associated  with  a  urine  which  is  acid,  contains  granular 
casts,  and  is  loaded  with  urates.     Thirdly,  they  have  been 
isolated  and  cultivated  from  the  urine  in  the  bladder  of  rabbits. 
Since  we  ascertained  these  facts  we  have  had  no  opportunity 
of  following  up  the  investigation  in  the  human  kidney.     The 
indications,  however,  seem  clear.     It  is  highly  probable  that 
the  kidney  takes  an  important  part  in  the  preservation  of 
the  organism  against  the  results  of  this  infection.     The  char- 
acter of  the  urine  in  rheumatic  fever,  the  occasional  occurrence 
of  nephritis,  possibly,  too  the  occurrence  of  infarcts,  together 
with  the  researches  of  Chvostek  and  Singer,  all  point  to  an 
investigation  on  these  lines  as  likely  to  produce  some  valuable 
facts.     Have  the  relapses  that  occur  so  frequently  any  depend- 
ence upon  the  condition  of  the  kidney  ?     Does  the  occasional 
association  of  gout  and  rheumatic  fever  bear  any  relation  to 
the  occurrence  of  renal  lesions  ?     These,  among  others,  are  the 
problems  that  suggest  themselves  to  us.     Finally,  the  acute 
nephritis  which  sometimes  occurs  in  childhood  without  any 
apparent  cause  may  possibly  find  its  solution  as  being  in  some 
instances,  the  result  of  this  infection. 

4.  Occurrence  in  the  liver.  In  the  rabbit  we  have  found  in 
the  liver  areas  of  coagulation  necrosis.  The  liver  cells  undergo 
a  rapid  de.-truction  and  the  micro-organisms  can  be 
di  monstrated  within  them.  In  this  organ  they  do  not  stain 
w<  11  and  our  examination  of  these  sections  leads  us  to  suppose 
that  they  are  destroyed  by  the  agency  of  the  liver  cells.  As 
yet  we  have  not  found  in  the  liver  of  the  rabbit  that  extreme 
vascular  engorgement  seen  in  rheumatic  fever,  but  the  hepatic 
venules  are  more  dilated  than  usual.  In  one  severe  case  of 
rheumatic  fever  we  found  the  condition  of  the  liver  cells 
n  embled  closely  that  found  in  the  rabbit,  and  we  believe  that  in 
this  <  ase  also  the  diplococci,  whose  presence  we  had  proved  by 
isolating  them  from  the  pericardial  fluid,  were  being  destroyed 
in  this  organ.  The  small  size  of  the  micro-organisms  and  the 
fact  that  they  stained  with  difficulty  does  not,  however,  permit 
as  yet  a  dogmatic  statement  upon  these  points. 

5.  Occurrence  in  the  joints.  We  have  no  personal  know- 
ledge of  their  occurrence  in  the  joints  in  the  human  being, 
but  Triboulet  discovered  a  diplococcus  in  the  joint  exudation. 


I 

•I  • 


^ 

* 


FIG. 24 


Section  of  pulmonary  alveoli  from  a  rheumatic  pneumonia  showing  (Z>)  diplococci. 
i  Zeiss,  obj.  j1.,  oc.  3.1 


THE  /ETIOLOGY  OF  RHEUMATIC  FEVER       127 

They  occur,  sometimes  in   vast  numbers,  in   the  exudation 
in  the  rabbit.     The   fluid  in  the   joints   of  rabbits   may  be 
clear  or  opaque  and  may  even  have  the  consistence  of  peri- 
cardial lymph.     This  thick  fluid  is  found  in  the  joints  that 
have   been  affected  for  some  time  and  such  joints  remain 
distended  with  this  fluid.     Possibly  this  may  be  thought  to  be 
an    important    difference    between    the    condition    produced 
artificially  in  rabbits  and  the  rheumatic  fever  of  man.     In  no 
single  case,  however,  have  we  found  suppuration  in  any  of  the 
viscera  associated  with  this  condition  of  the  joints  ;    further, 
the  exudation  is  definitely  fibri  no -cellular  in  character.     We 
lay  especial  stress  upon  this  point,  for  we  are  sure  that  to  come 
to  the  conclusion  that  this  condition  found  in  the  rabbit  was 
a  suppurative  one  simply  from  the  macroscopic  appearance 
of  the  exudation  would  be  an  error.     The  disease  must  be 
studied  both  clinically  and  pathologically  and  the  affected 
organs   examined    microscopically   before    pronouncing   upon 
the  nature  of  the  infection.     The  bursas  and  tendon  sheaths 
are  affected  in  the  neighbourhood    of   the  joint  in  rabbits  as 
in  man.     As  further  evidence  upon  the  question  of  suppuration 
the  following  experiment  is  of  value.     A  rabbit  was  inoculated 
under  the  skin  of  the  abdomen  with  the  contents  of  six  blood 
agar  tubes  of  a  virulent  culture.     A  large  firm  swelling  resulted, 
a  gigantic  nodule,  which-  increased  in  size  for  some  days  and 
then   gradually  subsided  without   any  indication  of   abscess 
formation.      There   were    no   symptoms    of    a    constitutional 
affection  and  except  for  this  slightly  tender  swelling  no  clinical 
symptoms  followed.     Apert,  in  a  similar  experiment  with  the 
diplococcus,  isolated    by  Triboulet  and  himself,  produced  a 
like  result. 

6.  Occurrence  in  the  lungs  and  pleura.  In  the  lungs  and 
pleurae  of  one  of  the  rabbits  that  had  been  killed  when  suffering 
from  pericarditis,  endocarditis,  pleurisy,  and  pneumonia  we 
demonstrated  diplococci  which  we  believe  to  be  identical  with 
those  found  in  the  other  viscera.  They  were  present  in  masses 
and  In  vast  numbers  beneath  the  visceral  pleura  and  in  the 
alveoli  of  the  lungs.  The  alveoli  were  filled  with  an  exudation 
resembling  very  closely  that  seen  in  lobar  pneumonia,  though 
the  exudation  had  a  less  reticular  arrangement.  In  a  case  of 
rheumatic  morbus  cordis  complicated  with  pneumonia  we 
have  also  demonstrated  diplococci  in  the  alveoli  of  the  lungs 


128      THE  ETIOLOGY  OF  RHEUMATIC  FEVER 

in  great  numbers.  More  than  this  we  are  not  prepared  to  state, 
for  the  organisms  were  not  isolated  in  this  ease,  and  it  cannot 
therefore,  be  asserted  that  they  were  identical  with  those  which 
we  have  found  in  rheumatic  fever.  When  it  is  called  to  mind 
how  frequently  both  pleurisy  and  pneumonia  occur  in  rheu- 
matism this  demonstration  of  numerous  diplococci  in  the 
lungs  and  pleurae  of  the  rabbit  is  suggestive. 

7.  Occurrence  in  the  throat.  This,  again,  is  of  considerable 
interest  and  some  of  the  facts  that  have  come  to  light  have 
a  close  bearing  upon  the  treatment  of  the  disease.  We  briefly 
recapitulate  here  the  most  important  of  the  results.  In  the 
first  place  we  have  in  one  case  found  after  death  both  tonsils 
large  and  inflamed  and  this  when  the  illness  had  been  one  of 
long  duration.  Before  death  there  had  been  an  exacerbation 
of  rheumatism  and  this  development  of  tonsillitis  is  known  to 
occur  not  only  at  the  commencement  but  also  during  the 
course  of  a  prolonged  rheumatic  attack.  In  a  film  from  the 
deeper  part  of  these  tonsils  we  found  diplococci  and  they 
were  also  present  in  the  sections  that  were  made  of  the  tonsils. 
Secondly,  in  none  of  the  rabbits,  all  of  which  were  injected 
intravenously,  was  there  any  inflammation  of  the  tonsils. 
Lastly,  we  isolated  diplococci  from  the  throat  of  an  adult  the 
subject  of  rheumatic  fever  who  was  suffering  from  an  acute 
faucial  catarrh.  These  micro-organisms  rapidly  produced  death 
in  a  rabbit.  After  death  endocarditis,  pericarditis,  and  cardiac 
dilatation  were  found  and  the  organisms  once  more  isolated. 
It  has  been  already  stated  that  many  observers  have  insisted 
upon  the  throat  as  an  important  site  of  infection  in  rheumatic 
fever,  and  these  facts  strongly  support  this  view.  Further, 
they  point  to  a  very  watchful  regard  for  the  throat  in  rheumatic 
patients  and  to  the  assiduous  treatment  of  it,  not  only  in  the 
acute  stage  at  the  commencement  of  the  illness,  but  also 
throughout  the  period  during  which  active  manifestations  of 
rheumatism,  other  than  angina  faucium,  are  present. 

8.  Occurrence  in  the  brain  and  its  membranes.  Our  facts 
with  regard  to  this  are  scanty,  but  coupled  with  the  observa- 
tions of  Dana,  Apert,  Westphal,  Wassermann,  and  Malkoff 
seem  worthy  of  record.  In  one  rabbit  after  the  subsidence 
of  arthritis  a  paresis  of  the  hind  limbs  ensued  which  lasted 
for  three  weeks.  Tins  was  one  of  our  earlier  cases  and  at 
tht:  time  we  hardly  grasped  the  significance  of  the  symptom. 


FIG. 


Film  of  pleural  exudation  from  a  rheumatic  pleurisy  showing  the  diplococei. 
i  Zeiss,  oh]'.  },,  oc.  3.) 

A.  Inflammatory  cells. 

B.  Fibrinous  exudate. 

C.  Micrococci. 


THE  ETIOLOGY  OF  RHEUMATIC  FEVER       129 

From  another  rabbit  which  died  from  severe  endocarditis  we 
isolated  the  diplococcus  in  pure  culture  from  the  fluid  in  the 
lateral  ventricles.  In  a  case  of  chorea  that  died  in  St.  Mary's 
Hospital  in  1898  in  which  the  movements  were  very  severe  and 
the  heart  but  little  affected  we  demonstrated  numerous 
diplococci  in  the  perivascular  lymph  spaces  of  the  pia  mater, 
in  its  capillaries,  and  also  in  some  parts  of  the  motor  area 
of  the  brain.  In  a  case  of  chorea  of  similar  type  we  demon- 
strated them  in  large  number  in  the  mitral  valve.  In  neither 
case,  however,  were  these  micro-organisms  isolated.  Diplococci 
have  also  been  discovered  in  chorea  by  Dana,  Apert,  and 
Wassermann,  and  in  Westphal's  case,  examined  by  Wasser- 
mann,  polyarthritis  was  produced  in  rabbits.  It  is  probable, 
then,  that  there  is  a  close  association  between  rheumatic 
chorea  and  the  occurrence  of  diplococci  in  the  brain  and  its 
membranes.  It  is  also  probable  that  the  frequency  of  the 
occurrence  of  chorea  in  childhood  depends  upon  the  more 
extensive  dissemination  of  these  micro-organisms  in  the 
young,  as  pointed  to  by  the  clinical  manifestations  of  the 
disease  at  this  age. 

VI.    The  Relation  of  Infective  to  Rheumatic 
Endocarditis 

It  is  clear  that  the  term  "infective  endocarditis,"  which 
has  for  some  time  been  under  suspicion,  can  now  no  longer 
be  used  in  contradistinction  to  "  rheumatic  endocarditis," 
for  both  are  plainly  infective.  The  relation  of  this  type  of 
heart  disease  to  that  found  in  rheumatism  has,  we  believe, 
been  made  much  clearer  by  this  investigation.  That  "  malig- 
nant endocarditis,"  as  we  prefer  to  name  it,  is  due  to  various 
causes  is  beyond  doubt,  but  the  frequent  association  of  this 
type  with  rheumatism  has  hardly,  we  think,  received  a  suffi- 
ciently minute  investigation.  It  is  indeed  thoroughly  recog- 
nised, but  the  explanation  of  its  occurrence  as  due  to  a  mixed 
infection  has  possibly  been  too  willingly  accepted. 

There  are  cases  which  have  the  history  and  many  of  the 
symptoms  of  rheumatic  fever  but  differ  in  the  progressive 
nature  of  the  valvulitis  and  in  the  occurrence  of  marked 
pyrexia,  frequent  infarction,  and  nephritis.  With  such  there 
may   be    no   suppuration.     These    cases   suggest   that   under 

9 


130      THE  ETIOLOGY  OF  RHEUMATIC  FEVER 

certain  circumstances  rheumatism  may  depart  from  its  usual 
type  and  yet  the  infection  be  still  rheumatic — a  view  which  is 
also  maintained  by  Professor  Litten  of  Berlin. 

We  can  offer  no  complete  explanation  of  this  alteration  in 
the  type  of  the  disease,  but  think  that  a  clue  may  be  found 
in  the  distribution  and  behaviour  of  the  diplococci  in  the 
cardiac  valves.  In  simple  rheumatism  they  are  not  found  at 
first  upon  the  surface  of  the  valve,  and  the  disease  tending, 
as  it  does,  to  recovery,  they  are  destroyed  by  phagocytosis, 
and  possibly  in  other  ways,  the  valve  itself  undergoing  sclerosis. 
In  the  malignant  type  they  reach  the  free  surface  and  then 
appear  to  multiply  with  great  rapidity,  for  they  are  found 
in  large  masses.  If  then  they  are  detached  by  the  force  of  the 
blood-stream  they  may  possibly  give  rise  to  a  condition  of 
rheumatic  septicaemia  recognised  clinically  as  malignant  endo- 
carditis. Why  they  should  overstep  the  barrier  of  the  endo- 
cardium in  this  way  we  do  not  know,  but  it  is  suggestive  that 
the  valves  have  usually  been  already  injured  by  a  previous 
rheumatic  attack  and  that  the  patient  is  usually  in  feeble 
health  at  the  time  of  the  final  infection. 

Finally,  we  must  say  that  throughout  this  investigation  we 
have  on  all  sides  received  the  greatest  help.  To  Mr.  H.  G. 
Plimmer  we  are  indebted  for  assistance,  criticism,  and  advice, 
and  we  can  only  express  our  obligation  by  claiming  to  be  his 
pupils.  The  physicians  at  St.  Mary's  Hospital  and  the  Hospital 
for  Sick  Children,  Great  Ormond  Street,  have  placed  their 
clinical  cases  at  our  disposal,  and  to  Dr.  H.  Thursfield,  the 
registrar  at  the  Children's  Hospital,  we  are  indebted  for  leave 
to  make  use  of  any  necropsies  that  might  be  of  service.  To 
Forbes  Tulloch,  a  student  of  St.  Mary's  Hospital,  we  are 
indebted  for  the  photo-micrographs.  This  generous  help  has 
greatly  lightened  the  labour  of  this  investigation  and  has  been 
an  additional  incentive  to  pursue  the  subject. 

REFERENCES 

1  Deutsche  Medicinische  Wochenschrift,  No.  46,  p.  809. 
"  ^Etiology  of  Acute  Rheumatism,"  Correspondenzblatt  fur  Schweizer 
Aerzte,  1892,  vol.  xxii. 

3  La  Semaine  Medicale,  1892,  No.  7,  p.  48. 

*  "  Experimental  Bacillary  Suppurative  Polyarthritis,"  Centralblatt 
fur  Bacteriologie,   1895,  Band  XIV,  p.  269. 


fi      .  -*v 


FIG.  26 

Section  through  crypt  of  tonsil  from  a  case  of  rheumatic  tonsillitis  showing 
diplococci.     (Zeiss,  obj.  ^,  oc.  3.) 

A.  Lymphoid  cells. 

B.  Diplococci. 


THE  ETIOLOGY  OF  RHEUMATIC  FEVER       131 

5  "  Infections  from  the  Pyogenic  Micro-organisms,"  Riforma  Medica, 
1894,  Nos.  6 j  to  68. 

6  Verhandlungen  des  Congresses  fur  Innere  Medicin,  1897,  p.  99. 

7  Wiener  Klinische  Wochenschrift,  1894,  No.  26,  p.  449. 

8  "  The  Microbic  Origin  of  Chorea,"  American  Journal  of  Medical 
Science,  1894,  p.  31. 

9  La  Semaine  Medicate,  1894,  p.  376. 

10  "  The  Role  of  the  Staphylococcus  in  Acute  Articular  Rheumatism," 
Archives  Generates  de  Medecine,  1894,  p.  513. 

11  Pathology,  1896. 

12  Deutsches  Archiv  fur  Klinische  Medicin,  1894,  vol.  liv,  p.  1,  "  The 
Bacteriology  of  Acute  Rheumatism." 

13  Clinical  Medicine,  vol.  ii,  p.  466. 

14  Lancet,  December  11,  1880,  p.  933. 

15  "  Harveian  Lectures  on  the  Rheumatism  of  Childhood,"  1888. 
10  Comptes  Rendus  de  la  Societe  de  Biologie,  1891. 

17  "  Sur  le  Rhumatisme  Articulaire  Aigu,"  Annates  de  VInstitut 
Pasteur,  1897. 

18  "  The  Results  of  Inoculation  of  a  Bacillus  obtained  from  a  Patient 
with  Rheumatic  Fever,"  La  Semaine  Medicate,  1896,  p.  376  ;  "The 
Microbe  of  Rheumatic  Fever,"  ibid.  p.  420  ;  "  The  Bacteriological 
Examination  of  the  Blood  in  Two  Patients  with  Rheumatic  Fever," 
Comptes  Rendus  de  la  Societe  de  Biologie,  1896,  p.  268  ;  "  A  Bacterio- 
logical Study  of  One  Case  of  Rheumatic  Fever,"  ibid.,  No.  30,  p.  882  ; 
"  The  Bacteriology  of  Rheumatic  Fever,"  ibid.,  No.  34,  p.  945. 

19  Comptes  Rendus  de  la  Societe  de  Biologie,  1898,  Tome  V,  p.  214. 

20  Bulletin  et  Memoir e  de  la  Societe  Medicate  des  Hopitaux,    1898, 

P-  93- 

21  Centralblatt  fur  Innere  Medicin,  1897,  Band  XVIII,  p.  825. 

22  Comptes  Rendus  de  la  Societe  de  Biologie,  1898,  Band  V,  p.  128. 

23  Archives  de  Medecine,  Tome  II,  No.  298. 

24  Aetiologie  und  Klinik  des  Acuten  Gelenkrheumatismus. 

25  "  Angina  in  Acute  Rheumatism,"  Miinchener  Medicinische  Wochen- 
schrift, 1899,  p.  28. 

26  Berliner  Klinische  Wochenschrift,  1899,  No.  29,  p.  638. 

27  Ueber  die  Maligne  (Nichtseptische)  Form  der  Endocarditis  Rheu- 
matica,  Berliner  Klinische  Wochenschrift,  1899,  No.  29,  p.  644. 

28  This  sentence  was  badly  expressed.  We  intended  to  convey  the 
fact  that  the  micrococcus  did  stain  by  Gram's  method,  but  did  not 
retain  the  colour  firmly. 


PAPER  NO.  IX 

THE  PATHOGENESIS  OF  RHEUMATIC 
FEVER 

(Reprinted  from  the  Transactions  of  the  Pathological  Society  of  London, 

1 901) 

The  first  part  of  the  original  paper  detailed  for  the  purposes  of 
practical  demonstration  the  experimental  results  we  had  recorded  in 
the  preceding  one.  This  has  been  omitted  and  only  the  part  dealing 
with  new  facts  is  published.  These  consist  of  an  addition  to  the 
number  of  cases  examined,  an  account  of  some  further  investigations 
with  the  diplococcus  isolated  from  the  tonsils  of  a  case  of  rheumatic 
sore  throat,  and  a  preliminary  note  upon  a  rabbit  that  had  shown 
choreiform  movements  as  a  result  of  inoculation.  Lastly,  an  explana- 
tion is  given  of  some  of  the  difficulties  met  with  in  the  demonstration 
of  the  diplococcus  in  the  tissues. 

Since  the  completion  of  the  preceding  paper,  we  have  obtained 
further  experimental  results  from  the  case  of  angina  faucium 
recorded  there  (vide  p.  107).  The  organisms,  isolated  from  the 
blood  and  cerebro-spinal  fluid  of  the  rabbit  that  had  developed 
rheumatism  as  a  result  of  inoculation  from  this  case,  were 
grown  in  the  usual  way,  and  the  cultures  from  six  tubes 
injected  intravenously  into  a  second  rabbit.  Three  days 
after  inoculation  the  hind  limbs  became  stiff  and  tender  ; 
there  was  wasting,  and  marked  increase  in  the  rate  of  the 
heart's  action.  Then  a  systolic  murmur  developed,  and  the 
knee-joints  became  swollen  and  tense  with  fluid.  This  marked 
effusion  persisted  for  a  week,  then  gradually  diminished,  and 
at  the  end  of  three  weeks  had  disappeared.  The  murmur, 
which  soon  vanished,  never  reappeared,  and  eventually  the 
animal  made  a  complete  recovery.  Thus  it  will  be  seen  this 
second  rabbit  passed  through  an  illness  characterised  by  poly- 
arthritis, with  possibly  also  endocarditis. 

132 


B 


— % 


♦  •« 


♦      • 


••  • 


^ 


FIG.    27 

Visceral  pericardium,  rheumatic  pericarditis   (man).      (Zeiss,  obj.  ^,oc.3.) 

A.  Cardiac  muscle.  C.  Diplococci. 

B.  Visceral  pericardium.  D  and  E.   Inflammatory  cells. 


FIG.  28 

The  viscera]  pericardium  of  a  rabbit  acutely  inflamed  as  the  result  of  the 
intravenous  inoculation  with  the  diplococcus.      (Zeiss,  obj.  fc,  oc.  3.) 
A.  Cardiac  muscle.  D.  Inflammatory  cells. 

R.  Visceral  pericardium.  E.  Connective-tissue  cells. 

('.    Diplococci. 

Compare  Fig.  2  7. 


PATHOGENESIS  OF  RHEUMATIC  FEVER       133 

We  have  also  increased  from  eight  to  eleven  the  number  of 
cases  of  rheumatic  fever  in  which  we  have  detected  the  diplo- 
cocci.  Two  of  these  were  not  favourable  for  further  investiga- 
tion. The  first,  an  adult,  died  during  the  hot  summer  weather, 
and  all  the  cultures  were  contaminated  with  B.  proteus  vulgaris. 
We  obtained  the  diplococci,  though  contaminated  in  this  way, 
from  the  bladder  after  death.  The  second,  a  child,  was  a 
chronic  case  with  recent  valvulitis,  and  the  growth  in  this  case, 
as  in  a  previous  case  of  the  same  nature,  was  feeble.  Our 
experience  with  cultures  from  the  valves  has  so  far  pointed  to 
the  difficulty  of  obtaining  a  satisfactory  growth  from  them. 
Cases  that  are  characterised  by  severe  pericarditis  are,  we  have 
found,  those  most  favourable  for  experimental  results. 

The  third  case,  a  child,  the  subject  of  repeated  attacks  of 
rheumatism,  was  admitted  to  St.  Mary's  extremely  ill  with 
severe  general  pericarditis.  Upon  two  occasions  the  urine  was 
obtained  with  strict  precautions,  and  mixed  with  the  acid 
medium.  Upon  the  second  occasion  a  pure  growth  of  the 
diplococci  was  obtained  and  sub-cultured  upon  blood  agar, 
and  the  cultures  from  four  tubes  injected  intravenously  into 
a  young  rabbit.  Three  days  after  inoculation  the  heart 
was  acting  extremely  rapidly,  and  we  felt  sure  there  must 
be  pericarditis.  The  joints  were  not  affected.  Then 
followed  slight  improvement,  but  nine  days  after  inoculation 
there  was  very  definite  pericardial  friction  and  considerable 
wasting.  This  friction  lasted  for  two  days,  the  heart  became 
feebler,,  the  sounds  spaced,  the  action  finally  irregular,  and 
death  occurred  upon  the  twentieth  day  from  cardiac  failure. 
One  joint,  the  right  knee-joint,  became  affected  during  the 
last  ten  days.  The  necropsy  showed  excess  of  pericardial 
fluid,  with  an  organising  exudate  adherent  to  the  visceral 
pericardium,  and  also  recent  mitral  and  aortic  valvulitis. 
It  is  of  interest  that  we  had  never  detected  an  endocardial 
murmur.  The  right  knee-joint  contained  an  opaque  oily  fluid  ; 
the  lungs  showed  some  basal  congestion.  The  spleen  was 
firm  and  not  enlarged  ;  the  liver  dark  ;  there  was  no  suppura- 
tion. The  left  kidney  was  very  large,  and  we  thought 
that  some  remarkable  complication  had  occurred,  but 
this  proved  to  be  due  to  the  congenital  absence  of  the  right 
kidney. 

The  film  made  from  the  pericardial  exudate  (which  was  shown 


134       PATHOGENESIS  OF  RHEUMATIC  FEVER 

under  the  microscope)  has,  we  believe,  cleared  up  one  of  the 
most  important  of  the  minor  difficulties  of  this  research — one 
which,  perhaps,  can  only  forcibly  appeal  to  those  who  have 
closely  investigated  the  microscopy  of  acute  rheumatism.  The 
detection  of  the  diplococcus  in  the  human  tissues  is  difficult, 
and  especially  difficult  in  the  valves.  Before  we  discovered 
them  we  had  repeatedly  seen  solitary  cocci,  both  in  the  peri- 
cardium and  inflamed  valves.  Later  we  also  found  that  if  the 
diplococcus  is  grown  upon  an  unsuitable  medium,  larger  solitary 
cocci  will  make  their  appearance. 

Finally,  in  this  pericardial  exudate,  which  had  commenced  to 
organise,  for  it  was  firm  and  distinctly  adherent,  we  found  a 
few  diplococci,  and  a  considerable  number  of  these  larger 
solitary  forms. 

The  inference  is,  we  think,  that  this  is  a  peculiar  condition 
of  these  organisms,  probably  dependent  upon  some  alteration, 
either  in  their  virulence,  or  in  the  chemistry  of  the  tissues  in 
which  they  are  located,  or  upon  both  factors.  How  much 
latent  energy  they  possess  while  in  this  form,  and  how  long  they 
may  persist  in  the  tissues,  we  are  unable  to  say,  though  from  the 
point  of  view  of  relapses  of  rheumatism  these  seem  important 
considerations.  If,  too,  these  larger,  solitary  cocci  and  this  dis- 
appearance of  the  diplococcal  forms  are  evidences  of  subsidence 
of  the  local  infection,  it  is  probable  that  a  great  local  activity 
of  the  infection  will  be  evidenced  by  the  converse — a  great 
increase  in  the  number  of  diplococci,  and  diminution  in  their 
size. 

The  last  experimental  result  to  which  we  make  reference  is 
important,  because  the  rabbit  manifested  for  three  days  the 
signs  of  chorea.  We  mentioned  previously  a  paresis  of  the 
hind  limbs  as  a  result  of  inoculation,  but  in  this  case  there  were 
sudden  involuntary  clonic  movements  of  the  limbs,  and  marked 
facial  twitching.  The  animal  was  extremely  nervous,  starting 
at  any  sudden  sound,  and  the  condition  at  once  forcibly  recalled 
the  well-known  characters  of  rheumatic  chorea.  Six  tubes 
of  a  culture  upon  blood- agar  had  been  injected  intra-venously, 
and  the  symptoms  developed  upon  the  fourth  day.  In 
addition  there  was  a  mitral  systolic  murmur.  We  killed  the 
animal  and  demonstrated  the  valvulitis,  but  we  have  not  as 
yet  investigated  the  brain  further  than  to  say  there  was  no 
meningitis.     To  recapitulate  : 


FIG.  29 

The  heart  and  lungs  of  a  rabbit  showing  ftbrino-plastic  pericarditis, 
the  result  of  infection  with  the  Diplococcus  rheumaticus. 


c 


FIG.  30 

Film  of  pericardial  exudation,  rheumatic  carditis,  showing  the  diplococci. 
(Zeiss,  obi.  ^h,  oc.  3.) 

A.  Inflammatory  cell. 

B.  Mass  of  diplococci. 

C.  Fibrinous  exudate. 


PATHOGENESIS  OF  RHEUMATIC  FEVER       135 

We  have  increased  the  number  of  our  observations  upon 
successive  cases  of  acute  rheumatism  from  eight  to  eleven, 
and  have  isolated  the  diplococcus  from  the  urine  during  an 
attack  of  acute  pericarditis.  We  have  also  produced  choreiform 
movements  in  a  rabbit  as  a  result  of  intravenous  inoculation 
and  traced  the  appearance  of  monococcal  forms  of  the 
diplococcus  in  a  healing  lesion  in  the  tissues. 

Finally,  it  appears  to  us  from  these  investigations  that 
rheumatic  fever  is  a  disease  characterised  by  great  local 
resistance.  The  diplococci  at  the  sites  of  the  local  lesions  are 
rapidly  destroyed.  Possibly  in  this  fact  lies  in  part  the 
explanation  of  the  fugitive  character  of  many  of  the  symptoms 
of  rheumatic  fever,  and  the  difficulty  of  finding  the  organisms 
in  the  tissues. 


PAPER  NO.  X 

THE  INFECTIVITY   OF  ACUTE   RHEUMATISM, 

WITH  ESPECIAL  REFERENCE  TO  CHRONIC 

ARTHRITIS  AND  RENAL  DISEASE 

(Reprinted  from  the  Clinical  Journal  May  1901) 

This  paper  was  read  at  a  discussion  held  by  the  Chelsea  Medical 
Society  in  igoi,  an  occasion  of  some  interest  because  it  was  the  first 
time  in  this  country  that  the  term  "  acute  infective  rheumatism  "  was 
used  as  an  official  title.  To  some  extent  it  was  a  resume  of  the  previous 
results,  and  only  the  new  points  which  were  touched  upon  are  given 
here.  These  were  the  occurrence  of  rheumatoid  and  osteo-arthritic 
changes  in  the  experimental  arthritis  and  the  possible  importance  of 
the  experimental  renal  lesions  in  directing  attention  to  renal  disease 
in  rheumatism. 

We  wish  to  bring  forward  some  further  investigations  that 
appear  to  us  to  throw  light  upon  chronic  arthritis  and  renal 
disease  in  rheumatism. 

We  have  repeatedly  demonstrated  the  diplococcus  in  the 
joint  exudation  in  rabbits,  and  have  also  found  them  in  the 
joints  in  human  rheumatism.  The  organisms  are  rapidly 
taken  up  by  endothelial  cells  and  polynuclear  leucocytes 
in  these  situations,  and  this  may  well  account  for  the  difficulty 
of  demonstrating  them  in  acute  rheumatic  arthritis,  which  is 
usually  of  less  severe  type  than  that  produced  experimentally 
in  the  rabbit.  The  presence  of  the  organisms  in  this  form  of 
arthritis  brings  acute  rheumatic  affections  of  joints  into 
line  with  arthritis,  the  result  of  septic,  gonorrhoeal,  and  pneu- 
monococcal  infections — according  to  the  researches  of  Drs. 
Bannatyne,  Wohlmann,  and  Blaxall,  rheumatoid  arthritis  must 
be  included  in  this  group  also.  Gouty  and  syphilitic  arthritis 
remain  as  examples  in  which  no  micro-organism  has  been 
demonstrated,  the  former,  perhaps,  not  being  the  result  of  a 

J36 


FIG.  31 


Section  of  a  gouty  tophus  under  a  low  power.     A  stellate  mass  of  biurate  of 
soda  crystals  is  seen  in  the  centre  of  the  nodule  surrounded  by  necrotic  tissue. 


<r 


i* 


>  * 


i 


\\\v\V    \\  v\        »\  , 


vSP 


FIG.    32 

Section  of  the  same  tophus  under  high  magnification  (Zeiss,  obj.  T\,  oc.  3),  showing-  peripheral 

striation  of  the  necrotic  tissue  in  which  there  is  biurate  of  soda.  The  appearance  strongly  suggested 

a  local  origin  of  the  biurate  of  soda  in  the  damaged  tissue. 


INFECTIVITY  OF  ACUTE  RHEUMATISM        137 

microbic  infection,  the  latter  almost  certainly  being  micro- 
organic. 

In  our  previous  investigations  a  joint  in  one  of  the  rabbits 
that  developed  polyarthritis  remained  in  a  chronic  state  of 
inflammation,  and  did  not  subside.  In  every  other  instance 
the  swellings  either  completely  subsided,  or  the  animal  died  from 
the  infection  ;  but  in  this  case,  though  the  animal  recovered 
except  for  some  slight  valvular  disease,  the  left  shoulder- 
joint  remained  swollen  and  slightly  tender  from  May  30  until 
October  8,  when  the  animal  was  killed.  Then  we  found  much 
gelatinous  swelling  of  the  connective  tissues  around  the  joint, 
with  thickening  of  the  capsule  and  erosion  of  the  cartilages.  This 
result  suggests  that  researches  in  this  direction  may  eventually 
throw  light  upon  the  more  chronic  forms  of  rheumatic 
arthritis. 

Another  point  to  which  we  wish  to  call  attention  is  the 
condition  of  the  kidneys  in  acute  rheumatism.  In  fatal  cases 
we  have  found  very  definite  changes  in  the  parenchyma, 
especially  of  the  convoluted  tubules.  There  is  marked  cloudy 
swelling  of  the  protoplasm  of  the  renal  cells  with  fatty  change, 
and  some  desquamation.  The  change  is  diffuse — that  is, 
it  affects  a  great  number  of  the  convoluted  tubules.  Further, 
we  have  isolated  the  diplococcus  from  the  urine  in  acute 
rheumatic  pericarditis,  and  recently  we  have  isolated  it  from 
the  kidney  and  urine  in  the  bladder  after  death. 

In  rabbits  the  kidneys  are  more  severely  affected,  but 
the  changes  are  of  the  same  type  ;  there  is  much  cloudy 
swelling  and  also  some  desquamation  of  the  renal  cells,  and 
in  their  kidneys  we  have  repeatedly  demonstrated  the  micro- 
organisms. Further,  in  the  rabbit  we  have  traced  this  con- 
dition step  by  step  to  the  formation  of  a  white  infarct,  which 
certainly  in  this  animal,  and  most  probably  in  man,  is  not 
always  the  result  of  a  gross  embolism,  but  of  the  invasion 
of  a  particular  area  by  a  considerable  number  of  the  diplo- 
cocci.  As  a  result  the  cloudy  swelling  in  that  area  passes 
into  the  stage  of  necrosis,  and  thus  is  produced  the  white 
infarct. 

It  appears  to  us  that  the  kidney  is  an  important  site  for 
elimination  of  the  poisons  produced  by  the  rheumatic  infection, 
and  that  in  this  process  the  kidney  itself  suffers  to  some  extent. 
Usually  the  injury  is  not  gross,  for  though  albuminuria,  and 


138        INFECTIVITY  OF  ACUTE  RHEUMATISM 

in  some  malignant  cases  hematuria  and  nephritis  occur  in 
this  disease,  as  a  rule  there  is  not  albuminuria  or  evidence 
of  serious  renal  inflammation. 

When  a  white  infarct  heals,  we  know  the  result  is  a  scar, 
and  it  is  possible  that  repeated  attacks  of  acute  rheumatism 
may  do  permanent  damage  to  the  renal  tubules,  not  of  the 
gross  nature  found  in  the  infarct,  but  of  a  grade  sufficient  in 
severity  to  destroy  the  functions  of  many  tubules,  and  perhaps 
lead  to  the  gradual  replacement  by  fibrous  tissue.  In  brief, 
repeated  attacks  of  acute  rheumatism  in  the  young  may  lead 
to  fibrosis  of  the  kidney  in  the  adult,  or,  short  of  that,  impair 
the  function  of  the  kidney  for  the  elimination  of  the  rheumatic 
poison  in  later  life.  As  a  result  of  this  it  may  be  that  a  sub- 
sequent attack  of  rheumatism  in  adult  life — though  less  severe, 
because  the  adult  is  less  susceptible — is  more  chronic,  because 
the  poisons  are  eliminated  with  more  difficulty. 

When  we  turn  to  gout  we  know  that  the  kidneys  suffer  much 
in  the  disease,  and  that  some  authorities  give  to  the  kidneys 
the  first  place  in  its  causation,  and  all  allow  the  impairment 
of  their  function  as  a  prominent  factor  in  the  more  chronic, 
inveterate,  and  cachectic  types. 

For  these  reasons  it  seems  to  us  important  to  study  the 
kidneys  very  closely  in  acute  rheumatism,  and  perhaps  it  may 
be  found  that  albuminuria  is  more  frequent  than  is  generally 
supposed,  or  that  the  peculiar  condition  of  cyclical  albuminuria 
may  sometimes  be  a  result  of  the  impairment  rather  than 
destruction  of  function  that  appears  to  be  the  result  of 
rheumatic  fever. 

The  last  point  we  touch  upon  is  concerned  with  malignant 
endocarditis.  We  have  now  collected  many  facts  to  show 
that  some  of  these  cases  are  truly  rheumatic,  and  not  the  result 
of  secondary  infections. 

This  suggests  by  analogy  that  some  of  these  lesions  of  joints 
that  run  on  to  ulceration  and  destruction  of  cartilage  may  be 
really  rheumatic.  The  disease  has  there  altered  in  type, 
and  for  some  reason  has  become  locally  malignant  in  these 
situations,  as  it  sometimes  becomes  in  the  valves.  This  we 
should  say  is  not  a  new  suggestion,  but  is  commented  upon  in 
the  classical  work  upon  pathology  by  Wilks  and  Moxon  and 
clearly  deserves  fresh  consideration. 


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PART  II 

SUB-GROUP  B 
THREE  PAPERS  UPON  ARTHRITIS 

XI.  OBSERVATIONS  UPON  THE  ARTHRITIS  PRODUCED  IN 
RABBITS  BY  THE  INTRAVENOUS  INOCULATION  OF  A 
DIPLOCOCCUS  ISOLATED  FROM  CASES  OF  RHEUMATIC 
FEVER 

XII.  AN   EXPERIMENTAL   PRODUCTION    OF    THE    OSTEO- 
ARTHRITIC  TYPE  OF  RHEUMATOID  ARTHRITIS 

XIII.  OBSERVATIONS  UPON  CERTAIN  FORMS  OF  ARTHRITIS 


139 


PAPER  NO.  XI 

OBSERVATIONS  UPON  THE  ARTHRITIS 
PRODUCED  BY  THE  INTRAVENOUS 
INOCULATION  OF  A  DIPLOCOCCUS 
ISOLATED  FROM  CASES  OF  RHEUMATIC 
FEVER 

(Reprinted  from  the  Transactions  of  the  Pathological 
Society  of  London  1901) 

We  had  two  objects  in  view  when  writing  this  paper.  The  first 
was  to  demonstrate  more  fully  and  decisively  than  we  had  heretofore 
the  constancy  and  reality  of  the  arthritis  produced  by  the  diplococcus. 
The  advisability  of  this  step  has  been  justified  by  subsequent  experience, 
for  the  repeated  failures  of  some  other  investigators  to  produce  any 
experimental  lesions  with  this  micrococcus  would  have  otherwise  made 
us  almost  fear  that  the  idea  might  arise  that  we  had  drawn  on  our 
imaginations  in  the  descriptions  of  our  results.  The  second  object 
was  to  place  on  a  scientific  basis  the  investigation  of  nonsuppurative 
arthritis  of  the  rheumatic  and  rheumatoid  types.  A  possibility  only 
to  be  realised  when  the  ability  to  obtain  such  lesions  by  intravenous 
inoculation  was  obtained.  Lastly,  in  this  paper  we  gave  our  reasons 
for  the  choice  of  the  name  "  diplococcus  rheumaticus." 

We  propose,  in  the  present  communication,  to  demonstrate 
the  nature  of  the  arthritis  which  is  produced  by  the  intravenous 
inoculation  into  rabbits  of  a  diplococcus  which  we  have  isolated 
from  eighteen  cases  of  rheumatic  fever. 

The  number  of  clinical  cases  that  we  have  investigated,  the 
constancy  of  the  experimental  results,  and  the  explanation 
they  afford  of  the  phenomena  of  the  disease,  appeal  to  us  as 
evidence  sufficiently  strong  to  warrant  the  name  Diplococcus 
rheumaticus  being  applied  to  this  organism. 

Guided  by  these  facts,  we  turn  now  to  the  study  of  the 
experimental  arthritis.  We  find  that  it  is  a  prominent  symptom 

141 


142  ARTHRITIS  PRODUCED 

in  the  disease  that  is  produced,  but  it  is  not  invariable.  For 
some  months  after  our  first  investigations  we  failed  to  observe 
the  occurrence,  but  latterly  we  have  again  met  with  a  consider- 
able number  of  examples.  It  must  not  be  thought  that  at  the 
time  we  failed  to  observe  arthritis  our  results  were  negative  ; 
on  the  contrary,  pericarditis,  valvular  disease,  or  both,  occurred 
with  remarkable  constancy.  In  its  varied  manifestations  the 
disease  produced  in  rabbits  resembles  the  rheumatic  fever 
of  childhood  rather  than  that  of  the  adult.  But  the  arthritis 
is  more  severe,  and,  without  losing  sight  of  the  distinction, 
between  a  serous  and  synovial  membrane,  we  would  compare  it, 
in  its  severity,  to  the  pericarditis  of  childhood. 

Thus  in  rabbits  we  have  found  clear  or  slightly  blood-stained 
effusions,  comparable  to  the  early  exudations  in  acute  peri- 
carditis, and  then,  again,  opaque  exudations  with  flakes  and 
fibrino-cellular  exudation,  such  as  are  so  frequently  seen  in 
the  rheumatic  pericarditis  of  childhood. 

These  conditions,  we  are  aware,  are  not  unknown  in  man,  to 
quote  from  the  classical  work  on  pathological  anatomy  by 
Wilks  and  Moxon.  Upon  this  subject  of  rheumatic  arthritis 
they  write,  "  Sometimes  you  find  the  joint  much  distended 
with  turbid  fluid,  and  its  surface  pink  from  congestion  of  the 
vessels.  In  other  cases  large  flakes  of  lymph  float  in  the 
fluid,  or  a  coating  of  lymph  is  found  lining  the  whole  of  the 
synovial  surface  of  the  joint.  .  .  .  Again,  it  is  not  only  within 
the  joints  that  you  see  evidence  of  inflammatory  action  in 
rheumatism,  but  also  in  the  sheaths  of  the  tendons.  We  have 
several  times  found  the  sheaths  of  the  extensors,  where  passing 
the  wrists,  full  of  the  same  turbid  flaky  fluid  as  was  present  in 
the  wrist-joints." 

In  rabbits,  also,  tenosynovitis  and  bursitis  may  be  observed, 
as  well  as  arthritis. 

Usually  several  joints,  and  these  the  larger  ones,  are  affected. 
The  third  day  is  the  most  usual  time  for  the  first  indication  to 
be  seen  of  arthritis,  but  a  week  or  longer  may  elapse,  and  the 
date  of  the  various  joint  infections  may  be  separated  by  an 
interval  of  some  days.  The  acute  arthritis  is  painful,  the 
swelling  may  be  slight,  or  the  joints  distended  with  fluid. 
Recovery  may  be  complete,  but  in  two  cases  one  joint  remained 
swollen  for  some  months.  When  the  animals  were  killed  we 
found  thickening  of  the  fibrous  tissues  of  the  joints,  and  a 
tenacious  fluid  resembling  unboiled  white  of  egg.     We  have 


FIG.  3o 

'he  left  shoulder-joint  of  a  rabbit  showing  rheumatic  arthritis 
tatural  size).  There  is  great  thickening  of  periarticular  tissues 
ud  joint  capsule,  the  result  of  an  arthritis  due  to  the  intravenous 
tjection  of  the  diplococcus.  The  cartilages  were  not  affected.  The 
xudation,  considerable  in  amount,  was  clear.  The  arthritis  was 
of  three  weeks  duration,  and  other  large  joints  were  affected. 


FIG.  36 
Experimental   rheumatic  arthritis  ;    film  of 
the  exudation  showing  a   delicate  fibrinous 
network    with    endothelial    cells  and  a  few 

leucocytes.     Diplococci  are  seen  in  the  endo- 
thelial cells. 


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FIG.   37 

Section  through  the  capsule  and  synovial  membrane  of  the  kneejoint  of  a  rabbit,  showing  experimental 
arthritis  the  result  of  intravenous  inoculation  with  the  diplococcus.     (Under  low  magnification.) 

A.  <  lonnective  tissue  of  the  capsule. 

B.  The  synovial  membrane  infiltrated  with  leucocytes. 

C.  Fibrino-cellular  exudation  on  the  surface  of  the  synovial  membrane. 

D.  .Muscular  fibres. 

Under  high  magnification  numerous  diplococci  were  seen  in  the  synovial  tissue  and  in  the  leucocytes. 


BY  INTRAVENOUS  INOCULATION  143 

rarely  observed  changes  in  the  bones  such  as  are  seen  in  chronic 
rheumatoid  arthritis. 

We  have  brought  for  demonstration  an  affected  and  a  healthy 
joint,  together  with  the  exudation  from  the  diseased  one, 
taken  from  a  case  which,  we  think,  must  be  considered  very 
striking.  The  culture  was  obtained  from  the  mitral  valve  of  a 
girl  aged  five  years,  who  died  in  the  Children's  Hospital, 
Great  Ormond  Street,  from  a  fatal  first  attack  of  rheumatic 
carditis.  The  demonstration  of  the  organism  from  a  fatal 
first  attack  of  rheumatic  fever  is  in  itself  an  important  point, 
and  has  a  vital  bearing  upon  the  question  of  rheumatic  fever 
considered  as  the  result  of  a  mixed  infection,  but  on  this  occa- 
sion it  must  be  sufficient  to  relate  the  experimental  investigation 
which  followed. 

Upon  April  16,  1901,  after  two  days'  incubation  in  a  medium 
of  ascitic  bouillon,  i|  c.c.  were  injected  intravenously  into 
a  rabbit.  Three  days  afterwards  there  was  a  slight  swelling 
of  the  left  fore-limb  ;  evident  swelling  of  the  left  shoulder- 
joint  quickly  followed,  remained  for  a  fortnight,  and  then 
commenced  to  subside.  The  heart  acted  with  great  rapidity, 
but  we  failed  to  detect  a  murmur,  though  the  animal  was 
short  of  breath  on  exertion.  The  rabbit  was  killed  three 
weeks  after  inoculation,  and  we  removed  in  a  sterilised  pipette 
some  of  the  fluid  from  the  joint. 

The  distension  of  the  joint  capsule  was  well  shown.  The 
early  mitral  endocarditis  and  marked  dilatation  of  the  left 
ventricle,  the  mottled  liver,  small  spleen,  and  pale  kidney 
(the  specimens  of  which  were  shown)  are  very  characteristic 
of  the  disease  in  the  rabbit. 

A  film  of  the  exudation  from  the  joint  shows  a  delicate 
fibrinous  network,  a  few  red  blood-corpuscles,  some  endothelial 
cells,  and  a  few  leucocytes.  Of  these  leucocytes  some  show 
numerous  coarse  granules  in  their  protoplasm,  staining  a  red 
colour  with  eosin  ;  others  show  no  such  granules.  In  some  of 
the  endothelial  cells  leucocytes  can  be  seen  in  various  stages 
of  destruction  ;  in  others  the  organisms  can  be  seen  in  the 
form  of  micrococci,  though  occasionally  a  diplococcal  form  is 
still  visible. 

In  another  case  of  arthritis  of  three  days'  duration,  the 
synovial  membrane  looked  to  the  naked  eye  almost  natural  ; 
the  fluid  was  blood-stained  and  contained  a  few  flakes.  The 
microscopic  section  of  the  synovial  membrane  was  of  interest, 


144    ARTHRITIS  BY  INTRAVENOUS  INOCULATION 

because  it  showed  in  the  delicate  areolar  tissue  which  binds  the 
endothelial  lining  to  the  fibrous  capsule  a  very  extensive  cellular 
exudation,  which  in  places  was  distinctly  fibrino-cellular.  In 
this  position  the  organisms  occur,  and  it  is  here  that  they  can 
be  found  in  rheumatic  synovitis.  It  is  easy  to  understand, 
after  a  study  of  the  section,  the  difficulty  there  is  in  obtaining 
a  culture  from  the  joint  in  a  rheumatic  arthritis  of  moderate 
severity,  for  the  reaction  is  great,  and  leucocytes  and  endothelial 
cells  rapidly  destroy  the  organisms.  The  acute  and  clear 
effusions  both  in  rheumatic  fever  and  in  experimental  arthritis 
are  usually  sterile. 

Another  interesting  feature  in  this  section  was  the  occurrence 
of  an  interstitial  cellular  exudation  between  the  fibres  of  the 
muscles  surrounding  the  joints.  This  may  throw  some  light 
on  the  muscular  pains  which  are  so  frequent  in  the  rheumatic 
fever  of  childhood. 

Under  a  third  microscope  there  is  a  section  demonstrating 
the  fibrino-cellular  type  of  exudation — that  which  we  compare 
to  the  plastic  type  of  pericarditis.  Leucocytes  which  stain  well 
and  are  not  necrotic  can  be  seen  lying  entangled  in  a  delicate 
fibrinous  reticulum. 

The  last  specimen  is  a  joint  showing  the  gelatinous  swelling 
of  the  fibrous  structures  which  occurs  in  the  acute  stage  of  the 
arthritis  ;  this  arthritis  was  produced  by  the  intravenous 
inoculation  of  a  culture  obtained  from  another  fatal  first  attack 
of  rheumatic  fever. 

To  summarise  :  Arthritis  in  rabbits  is  frequent  but  not 
invariable  in  its  occurrence.  It  is  a  polyarthritis,  affecting 
especially  the  larger  joints.  It  tends  to  recovery,  but  varies 
in  severity  ;  there  may  be  acute  swelling  of  the  fibrous  tissues 
of  the  joint,  which  become  gelatinous  in  appearance,  and  if  the 
condition  is  chronic  there  is  much  thickening  of  the  fibrous 
tissues.  The  exudation  varies  in  character  from  a  clear  or 
blood-stained  fluid  to  a  thick,  opaque,  fibrino-cellular  exudation. 
The  diplococcus  can  be  demonstrated  in  these  exudations, 
though  in  the  very  early  stages  they  are  absent  or  scanty,  and 
in  the  late  stages  they  are  either  destroyed  or  occur  in  the  form 
of  solitary  micrococci.  They  are  destroyed  by  leucocytes 
and  endothelial  cells,  and  they  probably  gain  access  to  the 
joint  through  the  minute  blood-capillaries  in  the  areolar  layer 
of  the  joint  capsule. 


FIG.   38 


Drawing  of  the  knee-joints  (natural  size)  of  the  rabbit  referred  to 
in  the  text.  The  left  knee-joint  (right  in  figure)  is  normal.  The  right 
knee-joint  shows  the  following  changes  :  (1)  The  articular  surface 
of  tbe  femur  is  thickened  and  the  cartilage  has  lo~t  lustre.  (2)  The 
edge  of  the  inner  condyle  is  rounded  and  there  i-  a  prominence  due 
to  a  new  formation  of  imperfect  bone  and  cartilage.  iSi  The  edge 
of  the  outer  condyle  is  rounded  and  lipped,  and  there  is  an  area  in 
which  there  is  a  destruction  of  bone  and  cartilage.  (4)iThe 
articular  surface  of  the  tibia  is  flattened,  the  edgesare  much  thickened 
and  the  cartilage  ha-  lost  gloss  (the  cartilage  when  the  specimen 
was  Eresh  had  a  pitted  appearance).  (5)  At  the  posterior  aspect  of 
the  outer  faeet  of  the  tibia  there  is  a  small  area  where  the  cartilage 
was  dettroyed  (this  can  hardly  be  seen  in  the  figure).  (6)  The 
crucial  ligaments  are  swollen  and  have  lost  their  lustre. 


PAPER  NO.  XII 

AN    EXPERIMENTAL  PRODUCTION    OF    THE 
OSTEO-ARTHRITIC  TYPE  OF  RHEUMA- 
TOID ARTHRITIS 

(Reprinted  from  the  Transactions  of  the  Pathological  Society  of  Londo  i, 

1902) 

This  paper  has  a  special  interest  in  being,  so  far  as  we  are  aware, 
the  first  record  of  an  osteo-arthritis  produced  experimentally  by  the 
intravenous  inoculation  of  a  micrococcus  isolated  from  a  case  of 
human  osteo-arthritis. 

Although  this  is  but  a  short  communication,  the  result  is  clearly  one 
of  fundamental  importance,  and  opens  up  the  field  of  study  of  chronic 
nonsuppurative  arthritis.  This  result  has  an  added  interest  when 
it  is  compared  with  those  which  we  produced  later  with  the  diplococcus 
rheumaticus.     Vide  Paper  XX. . 

Upon  July  16,  1901,  a  man  aged  67,  who  had  taken  carbolic 
acid  by  misadventure,  was  admitted  unconscious  to  St.  Mary's 
Hospital,  and  died  upon  the  18th. 

At  the  necropsy  we  found  that  several  of  his  joints  were 
crippled  by  a  chronic  destructive  arthritis  ;  this  was  especially 
the  case  with  the  tarsal  joints  of  the  left  foot,  the  left  knee- 
joint,  the  terminal  phalangeal  joint  of  the  right  index  finger. 
On  movement  of  the  knee  there  was  grating.  The  joint  con- 
tained two  drachms  of  a  clear,  glassy,  straw-coloured  fluid, 
in  which  floated  a  fewT  flakes  of  exudation.  The  structures  of 
the  articulation  were  much  diseased  ;  the  synovial  membrane 
was  much*  thickened,  and  in  places  hypersemic  ;  the  cartilage 
over  the  outer  facet  of  the  patella  was  completely  destroyed, 
as  also  in  great  part  those  over  the  articular  surfaces  of  the 
tibia  and  femur.  When  the  cartilages  had  not  been  destroyed 
they  had  lost  their  gloss.  The  bones  were  eburnated  at  the 
points    of    pressure.     The    fibrous    capsule    was    moderately 

145  10 


146  OSTEO-ARTHRITIC  TYPE  OF 

thickened,  but  the  changes  were  essentially  within  the  joint 
itself.  Lastly,  floating  in  the  synovial  fluid  was  a  loose  body, 
the  size  and  thickness  of  a  threepenny  piece,  probably  formed 
by  the  organisation  of  inflammatory  exudation. 

The  condition  was  clearly  one  of  non-suppurative,  chronic, 
destructive  arthritis.  The  extensive  erosion  of  the  cartilages 
and  the  eburnation  of  the  ends  of  the  bones  separated  it  from  the 
group  of  chronic  simple  rheumatic  arthritis.  In  the  ordinary 
sense  of  the  word,  it  was  not  a  gouty  joint,  for  there  was  no  de- 
posit of  biurate  of  soda  ;  from  the  character  of  the  fluid  it  could 
not  be  called  a  suppurative  arthritis.  It  must  therefore  be 
classified  among  those  chronic  destructive  joint  lesions  included 
under  the  name  of  rheumatoid  arthritis,  and  among  those 
in  that  group  which  we  especially  associate  with  later  life. 
The  cardiac  valves  were  normal,  and  there  was  nothing  dis- 
covered post  mortem  to  show  that  the  patient  had  suffered  from 
previous  attacks  of  rheumatic  fever. 


The  Microscopic  and  Bacteriological  Investigation 

A  few  diplococci  were  found  in  a  film  made  from  the  exudation 
in  the  knee-joint. 

Some  pieces  of  the  synovial  membrane  were  fixed  in  per- 
chloride  of  mercury,  and  others  incubated  in  the  acid  milk 
medium  that  we  have  used  for  the  culture  of  the  diplococcus 
of  rheumatic  fever. 

The  sections  that  were  cut  of  the  incubated  and  unincubated 
synovial  membrane  showed  the  presence  of  diplococci  situated 
especially  in  the  fringes. 

The  cultures  showed  a  growth  of  diplococci  and  of  the  Bacillus 
coli  communis. 

The  diplococcus  was  isolated  on  blood  agar  plates  and  trans- 
ferred to  blood  agar  tubes. 

Experimental  Results 

I.  Upon  July  24,  1901,  the  cultures  from  two  blood-agar 
tubes  were  injected  intravenously  into  a  rabbit.  Two  days 
afterwards  there  was  arthritis  of  the  left  carpus,  later  arthritis 
of  the  left  shoulder,  and  then  of  both  knee-joints.  There  was 
no  clinical  evidence  of  morbus  cordis. 


FIG.   39 


FIG.  40 


A  dissection  of  the  hind  limbs  of  the  rabbit,  the  inner  aspect  of  each  limb  is  represented 

1  ig.  40  shows  the  atrophy  of  the  muscles  of  the  right  limb.     Fig'.  39  shows  the  normal 

size  of  the  corresponding  muscles. 


RHEUMATOID  ARTHRITIS  147 

The  animal  was  killed  upon  August  8,  and  a  white  fluid 
containing  flakes  of  exudation  was  found  in  each  of  the  affected 
joints.  In  the  films  diplococci  were  demonstrated,  and  the 
leucocytes  stained  well  and  were  not  necrotic. 

There  was  no  erosion  of  the  cartilages,  the  heart  was  not 
affected,  and  there  were  no  visceral  lesions. 

Thus  from  the  first  inoculation  a  severe  multiple  arthritis  had 
resulted. 

II.  Upon  July  30  another  intravenous  inoculation  was  made 
into  a  rabbit. 

Throughout  September  nothing  was  noticed  but  some 
slight  wasting  of  the  right  hind  limb.  The  first  week  in 
October  we  found  a  slight  excess  of  fluid  in  the  right  knee- 
joint. 

The  remarkable  feature  of  this  case  was  the  definite  atrophy 
of  the  muscles  of  the  thigh  and  leg.  At  the  end  of  September 
the  limb  was  practically  useless,  and  the  atrophy  very  obvious. 
In  the  second  week  of  October,  ten  weeks  after  inoculation,  as 
there  seemed  a  slight  recovery  of  power  in  the  limb,  we  killed 
the  animal. 

There  were  no  visceral  lesions,  but  the  right  knee,  the  only 
joint  affected,  contained  a  slight  excess  of  a  clear  fluid,  part  of 
which  was  preserved  in  a  sterilised  pipette,  and  part  of  which 
was  used  for  inoculation  of  a  culture  tube.  The  right  knee- 
joint  was  enlarged,  and  the  articular  surfaces  distinctly 
though  slightly  flattened.  The  edges  of  the  articular  surfaces 
were  rounded,  and,  if  compared  with  the  corresponding  joint, 
will  be  seen  to  be  thickened,  as  the  result  of  some  lipping. 
A  thickening  on  the  inner  condyle  of  the  femur  was  especially 
noteworthy. 

In  two  places  on  the  outer  condyle  of  the  femur  the  bone  was 
eroded  and  the  cartilage  destroyed. 

There  was  both  bone  formation  and  bone  destruction. 
The  cartilage  on  the  tibia  had  lost  the  natural  gloss,  and  with 
a  lens  was  seen  to  be  roughened  and  pitted. 

There  was  also  on  the  outer  side  of  the  epiphysial  cartilage  of 
the  tibia  at  its  posterior  limit  a  small  erosion  with  destruction 
of  cartilage. 

The  atrophy  of  the  muscles  around  the  joint  was  very 
evident ;  the  muscles  on  the  anterior  and  posterior  aspects  of 
both  leg  and  thigh  were  affected. 


148  OSTEO-ARTHRITIC  TYPE  OF 

The  joint  capsule  was  not  greatly  thickened,  but  the  ligaments, 
especially  the  crucial,  were  opaque  and  swollen. 

The  culture  from  the  joint  was  sterile. 

Thus  in  this  case  there  resulted  from  an  intravenous  inocula- 
tion of  a  diplococcus,  isolated  from  a  case  of  chronic  rheumatoid 
arthritis,  a  monarticular  arthritis,  with  excess  of  clear  fluid  in 
the  joint  cavity,  erosion  of  cartilage  and  bone,  alteration  in 
the  shape  of  articular  surfaces,  and  marked  atrophy  of  the 
muscles  in  the  neighbourhood.  The  injury  to  the  joint  was 
therefore  of  the  nature  of  an  osteo-arthritis  rather  than  a 
synovitis  and  capsulitis  such  as  we  have  observed  in  the  experi- 
mental arthritis  produced  by  the  diplococcus  of  rheumatic 
fever. 

The  view  that  some  cases  of  rheumatoid  arthritis  are  of 
microbic  origin  has  been  long  maintained,  and  as  early  as 
1893  Max  Schuller  described  the  occurrence  of  bacilli  which 
exhibited  polar  staining  as  present  in  the  joint  exudations, 
and  various  investigators  have  contributed  to  our  knowledge 
of  the  bacteriology  of  rheumatoid  arthritis.1 

For  example,  in  this  country  the  researches  of  Bannatyne, 
Wohlmann,  and  Blaxall,  published  in  1896,  are  well  known.2 
The  organism  described  by  them  was  also  a  bacillus  which  was 
cultivated  by  Dr.  Blaxall. 

Chauffard  and  Raymond,  later,  in  1896,  also  isolated  a  diplo- 
bacillus  from  the  synovial  fluid  and  scrapings  of  the  lymphatic 
glands,  but  failed  to  obtain  cultivations.3 

In  1898,  von  Dungern  and  Schneider  isolated  a  minute  diplo- 
coccus from  a  case  of  rheumatoid  arthritis  which  had  apparently 
followed  rheumatic  fever.4  This  diplococcus  injected  directly 
into  the  knee-joint  of  a  rabbit  produced  changes  which  they 
believed  to  be  rheumatoid. 

In  this  investigation  of  ours  it  is  an  interesting  point  that  a 
monarthritis  of  this  type  should  have  followed  an  inoculation 
into  the  general  blood-stream.  Whatever  the  cause  or  causes  of 
rheumatoid  arthritis  may  be,  this  appears  to  be  quite  certain  : 
that  if  it  is  the  result  of  any  infection  the  paths  of  access  are 
far  distant  from  the  joints,  and  these  structures  are  damaged 
because  they  are  peculiarly  susceptible,  and  not  because  there  is 
direct  invasion  by  micro-organisms  as  in  traumatic  arthritis,  the 
result  of  a  punctured  wound. 


fig.  n 

Section  through  the  synovial  membrane  of  the  knee-joint  from  a  case  of  osteo- 
arthritis, showing  diplococci.     (Zeiss,  obj.  ^  oc.  3.) 


FIG.  42 

Section  through  the  synovial  membrane  of  the  knee-joint  of  the  same  patient  as  Fig.  41. 

The  tissue  had  been  incubated  for  twenty-four  hours  in  the  acid-milk  and  bouillon 

medium.    Showing  diplococci.     (Zeiss,  obj.  T\,  oc.  3.) 


RHEUMATOID  ARTHRITIS  149 

To  Summarise  the  Conclusions. 

1.  A  diplococcus  was  present  in  the  synovial  membrane  of 
the  knee-joint  of  a  man  aged  67,  several  of  whose  joints  showed 
the  chronic  destructive  changes  recognised  as  occurring  in 
one  type  of  rheumatoid  arthritis. 

2.  This  diplococcus  was  isolated  and  cultivated  in  pure 
growth,  both  on  blood  agar  and  in  a  medium  of  milk  and 
bouillon  acidified  with  lactic  acid. 

3.  Upon  two  occasions  when  injected  into  rabbits  it  produced 
a  severe  arthritis  but  no  cardiac  lesion. 

4.  The  organism  was  isolated  from  the  exudation  occurring 
in  the  joints  of  the  rabbit. 

5.  In  the  second  instance  a  monarthritis  resulted  from  the 
intravenous  inoculation,  which  showed  destruction  and  forma- 
tion of  bone  and  cartilage  with  some  flattening  and  lipping  of 
the  articular  ends  and  definite  wasting  of  the  muscles  in  the 
neighbourhood. 

The  capsular  structures  were  little  affected  and  the  exudation 
was  clear  and  sterile. 

6.  This  arthritis  differed  in  type  from  that  which  we  have 
hitherto  produced  with  the  diplococcus  of  rheumatic  fever. 

We  conclude,  therefore,  that — 

7.  This  diplococcus  was  the  cause  of  the  arthritis  in  the  case 
from  which  it  was  isolated,  and  of  the  condition  produced  by 
experiment  in  the  rabbit. 

REFERENCES 

1  Max  Schiiller,  Verhandlungen  des  funfzehnten  Cong.  f.  innere  Med. 
S.  127,  1892  ;   Berliner  klinische  Wochenschrift,  1896,  vol.  xxx,  p.  865. 

2  Bannatyne,  Wohlmann,  and  Blaxall,  Lancet,  1896,  vol.  i,  p.  1120. 

3  Chauffard  and  Raymond,  Revue  de  Medecine,  1896,  vol.  xvi,  p.  345. 

4  Von  Dungern  and  Schneider,  Munchener  med.  Woch.,  October  25, 


PAPER  NO.  XIII 

OBSERVATIONS    UPON    CERTAIN    FORMS    OF 
ARTHRITIS 

(Reprinted  from  the  British  Medical  Journal,  November  i , 

1902.) 

In  this  communication  the  results  of  the  previous  researches  into 
the  pathology  of  arthritis  are  applied  to  clinical  investigation  with 
the  object  of  directing  attention  to  the  importance  of  a  detailed  study 
of  the  exudations  in  arthritis.  An  attempt  is  made  in  it  to  put  into 
their  correct  perspective  the  results  of  the  preceding  paper,  with  par- 
ticular reference  to  those  conditions  generally  termed  "  rheumatoid 
arthritis." 

The  pathology  of  arthritis  has  of  recent  years  attracted  con- 
siderable attention,  and  surely,  though  perhaps  it  may  be 
slowly,  we  are  being  led  to  a  more  thorough  knowledge  of 
the  morbid  changes,  and  in  consequence  to  a  broader  view  of 
the  treatment  of  such  cases.  If,  then,  in  this  paper,  we  refer 
especially  to  our  own  investigations,  we  would  not  have  it 
thought  that  we  are  unaware  or  forgetful  of  the  work  of  others. 
We  do  so,  because  the  time  at  our  disposal  is  necessarily 
limited,  and  can  be  put  to  a  better  use  by  a  reference  to 
our  own  observations  than  by  making  quotations  from  the 
investigations  of  others  of  which  we  have  ourselves  no  personal 
knowledge. 

The  types  of  arthritis  to  which  especial  attention  will  be 
directed  are  the  rheumatic,  the  rheumatoid,  and  septic, 
although  incidentally  other  types — for  example,  those  which 
result  from  infection  with  the  pneumococcus  and  the  gono- 
coccus — will  need  a  passing  mention. 


150 


FIG.  43 

A  section  through  the  synovial  membrane  from  the  knee-joint  of  a  girl  who  died 

from  rheumatic  carditis,  showing  the  diplococci  in  the  areolar  tissue.     Daring  life 

the  knee  had  lieen  slightly  swollen  and  tender.     The  exudation  was  clear  except 

for  a  few  flakes  ;  from  it  the  diplococcus  was  isolated  in  pure  culture. 


».w 


,-/ 


-  '  t" 


«&/ 


•■•^■■-  l 


*     *•'*. 


&, 


FIG.    44 

Film  of  the  exudation  from  the  knee-joint  of  a  boy  suffering  from  rheumatic 

arthritis.     -V   special    feature  of   interest  is  the  great  number  of  diplococci 

present  in  the  exudation.     Complete  recover}  resulted. 


CERTAIN  FORMS  OF  ARTHRITIS  151 

Rheumatic  Arthritis 

In  the  Lancet  of  September  1900,  we  recorded  in  a  paper 
upon  the  etiology  of  rheumatic  fever  the  following  experimental 
results  : 

A  man,  aged  28,  came  to  St.  Mary's  Hospital  in  June  1900 
suffering  from  a  "  sore  throat."  His  illness  had  commenced 
with  malaise  and  pains  in  the  limbs  and  joints.  Four  years 
before  he  had  passed  through  a  severe  attack  of  rheumatic 
fever,  which  had  left  both  the  mitral  and  aortic  valves  dam- 
aged and  incompetent.  The  catarrh  and  injection  of  the 
throat  were  such  as  are  met  with  frequently  in  rheumatic 
angina.  The  heart  was  excited  and  dilated,  and,  after  his 
admission  into  the  hospital,  the  man  had  another  attack  of 
rheumatic  fever.  By  means  of  plate  cultures  we  isolated  from 
the  tonsils  some  minute  diplococci  which  resembled  those  we 
had  already  isolated  from  seven  cases  of  rheumatic  fever,  and 
which  had  been  obtained  from  various  tissues — from  the  peri- 
cardial effusions,  the  cardiac  valves,  and  the  blood  of  the 
living  patient.  An  intravenous  injection  into  a  rabbit  from 
the  blood  agar  cultures  resulted  in  the  death  of  the  animal 
from  mitral  endocarditis,  pericarditis,  pleurisy,  and  pneu- 
monia. The  diplococcus  was  isolated  from  this  animal,  and 
from  an  injection  into  a  second  there  developed  a  polyarthritis, 
from  which  after  three  weeks  the  rabbit  completely  recovered. 

It  is  evident  that  a  patient  suffering  from  rheumatic  fever 
harboured  in  his  throat  numerous  minute  diplococci  which 
were  capable  of  producing  in  an  animal  symptoms  indistin- 
guishable from  those  from  which  the  patient  himself  was  a 
sufferer. 

It  has  always  appeared  to  us  that  these  results  have  a  very 
important  bearing  on  the  study  of  rheumatic  arthritis,  and  we 
were  glad  to  find  that  a  physician  of  the  experience  and 
position  of  Dr.  Stephen  Mackenzie,  and  moreover  an  authority 
on  rheumatic  fever,  has  also  believed  them  to  be  valuable,  and 
has  alluded  to  them  in  his  recent  and  most  suggestive  oration 
to  the  Medical  Society  of  London.  Fritz  Meyer,  at  Berlin 
in  1901,  has  also  confirmed  in  many  points  these  results, 
on  a  more  extensive  scale  and  quite  independently,  and  the 
early  researches  of  Loeffler  on  the  streptococcus  articulorum 
must  also  be  mentioned. 


152  OBSERVATIONS  UPON 

The  ability  to  produce  experimental  arthritis  has  enabled  us 
to  study  various  phases  of  rheumatic  arthritis,  and  to  support 
our  clinical  facts  by  investigations  of  this  nature.  The  morbid 
processes  in  this  form  of  arthritis  seem  to  us  to  run  the 
following  course. 

The  micro-organisms  first  gain  access  to  the  synovial 
membranes  by  means  of  the  blood  stream,  and  then  make 
their  way  out  of  the  blood  capillaries  which  lie  in  the  areolar 
tissue  immediately  under  the  endothelium  which  bounds 
the  synovial  cavity.  This  endothelium  serves  as  a  barrier 
to  their  escape  into  the  cavity  of  the  joint,  and  the  cells 
which  are  phagocytic,  can  sometimes  be  seen  to  have  pro- 
liferated in  response  to  the  infection.  Further,  into  the 
areolar  tissue  in  which  the  diplococci  are  located  there  migrate 
a  large  number  of  leucocytes,  and  they  also  assist  in  the 
destruction  of  the  invader.  On  the  other  hand,  the  micro- 
organisms rapidly  exert  an  injurious  effect  upon  the  tissues. 
The  blood  capillaries  are  distended,  and  may  rupture,  the 
connective  tissues  are  swollen,  and  into  the  cavity  of  the 
joint  there  is  exuded  a  clear  or  blood-stained  fluid.  Yet  while 
the  endothelium  is  intact  the  micro-organisms  do  not,  at  any 
rate  in  any  number,  escape  into  the  fluid,  and  as  our  experi- 
ence has  repeatedly  shown,  these  early  exudations  are  often 
sterile. 

We  would  emphasise  that  this  escape  of  the  micro-organisms 
into  the  joint  cavity  is  a  vital  and  not  a  passive  process — one, 
therefore,  which  not  only  is  difficult,  but  which  may  not 
even  be  successful.  Indeed,  the  realisation  of  this  truth  is, 
we  believe,  of  far-reaching  importance  in  the  study  of  rheumatic 
affections. 

As  a  rule  the  morbid  changes  in  rheumatic  arthritis  go  no 
further  ;  the  micro-organisms  are  destroyed,  the  exudation  is 
absorbed,  and  the  function  of  the  joints  is  restored.  Yet 
sometimes,  as  we  know,  the  arthritis  may  be  more  severe, 
and  then  the  periarticular  tissues  become  swollen,  the  tendon 
sheaths  in  the  neighbourhood  are  implicated,  and  the  skin 
over  the  articulations  is  red  and  hot.  Then,  too,  the  fluid  in 
the  joints  becomes  turbid,  and  layers  of  fibrino-cellular 
exudation  may  line  the  cavities.  In  such  cases  the  endo- 
thelium is  damaged  and  the  diplococcus  can  be  isolated 
from  the  effusion  in  which  it  clings  closely  to  the  fibrinous 


\ 


Sfe'*<& 


FIG.  4.". 

Section  through  tlie  synovial  membrane  of  a  rabbit  with  experimental  rheumatism, 

showing  early  perivascular  exudation.     (High  power.) 


t  <         :S 


'"';  if  A 


FIG.  46 
Chronic  rhenmatic  arthritis  (human),  showing  perivascular  fibrosis  in  the  synovial 

uieuihraue.     (Low  power,  i 


CERTAIN  FORMS  OF  ARTHRITIS  153 

strands.  For  a  long  time  the  joint  remains  stiff,  but  as  a  rule 
the  bones  and  cartilages  are  not  damaged  to  any  great  extent, 
and  experience  has  shown  that  assiduous  after-treatment 
often  results  in  a  complete  recovery. 

There  is  another  type  of  rheumatic  arthritis  not  so  acute 
as  the  one  that  has  just  been  mentioned,  but  more  stubborn 
and  intractable,  and  in  these  cases  another  series  of  morbid 
changes  is  superadded.  These  changes  are  such  as  are  met 
with  in  all  chronic  rheumatic  lesions,  and  they  can  be  well 
studied  in  the  myocardium.  Around  the  blood  capillaries 
and  arterioles  there  is  at  first  a  cellular  exudation,  and  later 
a  perivascular  fibrosis.  This  newly  formed  fibrous  tissue 
around  these  small  blood  vessels  obeys  the  usual  rule,  and 
slowly  contracts,  diminishing  thereby  the  blood-supply  and 
nutrition  of  the  synovial  tissues.  We  have  on  several 
occasions  commented  upon  this  perivascular  fibrosis,  which 
it  may  be  said  is  in  no  way  peculiar  to  rheumatic  fever,  but 
we  are  indebted  to  Dr.  Chalmers  Watson  for  pointing  out  to 
us  its  importance  in  chronic  rheumatic  arthritis.  This  occur- 
rence may  in  part  explain  the  feeble  circulation  in  such  joints, 
the  dropsical  character  of  the  effusion,  and  the  slow  and 
imperfect  reaction  to  all  methods  of  treatment.  It  must  not 
be  forgotten  that  in  the  effusions  which  are  passive  rather 
than  active  no  micro-organisms  may  be  present,  and  the 
cultures  therefore  be  often  negative. 

These  three  types  of  arthritis  are  generally  recognised  by 
English  authorities  as  rheumatic  rather  than  rheumatoid  in 
nature,  though  it  must  be  admitted  that  these  two  conditions 
approach  one  another  very  closely,  a  point  to  which  we  shall 
allude  again. 

An  Infantile  Arthritis  described  by  Dr.  G.  F.  Still 

The  next  group  of  cases  is  a  very  interesting,  though  some- 
what rare  form  of  arthritis  in  childhood,  which  has  been 
admirably  described  by  Dr.  G.  F.  Still.  This  is  of  a  chronic 
type,  the  changes  are  periarticular  rather  than  intra-articular, 
the  lymphatic  glands  are  enlarged,  as  also  the  spleen.  In 
fatal  cases  general  adhesion  of  the  pericardium  has  on  more 
than  one  occasion  been  discovered  after  death,  and  this 
without  endocarditis.  Dr.  Parkes  Weber,  who  brought  such 
a  case  before  the  Medical  Society  of  London  this  year,  was  of 


154  OBSERVATIONS  UPON 

opinion  that  this  was  a  form  of  infantile  rheumatism.  Many 
observers  believe  this  group  to  be  a  form  of  rheumatoid 
arthritis,  while  others  suspend  their  opinion.  We  had  an 
opportunity  of  investigating  Dr.  Weber's  case  during  life,  but 
the  result  was  negative.  Such  a  negative  result,  however, 
means  little  or  nothing,  and  there  can  be  but  slight  room  for 
doubt  that  this  type  of  arthritis  is  of  bacterial  origin,  and  the 
likelihood  is  increased  by  the  fact  that  from  cases  of  rheu- 
matoid arthritis  with  enlarged  lymphatic  glands.  Chauffard 
and  Raymond  from  scrapings  of  these  glands  isolated  diplo- 
bacilli.  We  would  add  that  the  lymphatic  glands  are  some- 
times enlarged  in  the  neighbourhood  of  the  inflamed  joints 
produced  by  experimental  intravenous  inoculation  of  rabbit 
with  the  diplococcus  of  rheumatic  fever. 

Rheumatoid  Arthritis 

The  mental  transition  from  these  cases  to  those  of  rheumatoid 
arthritis  is  easy,  but  the  difficulties  that  surround  the  study 
of  the  latter  are  very  great.  One  of  the  difficulties  which  at 
once  meets  an  investigator  is  uncertainty  in  the  limitation  of 
the  disease.  Is  rheumatoid  arthritis  a  special  constitutional 
disease,  in  which  the  arthritis  is  a  prominent  feature,  com- 
parable, as  it  were,  to  the  carditis  of  rheumatic  fever,  or  is  it 
a  collection  of  morbid  conditions  with  these  features  in  com- 
mon— a  severe  and  intractable  arthritis,  accompanied  with 
much  muscular  wasting  ?  So  far  as  the  arthritis  is  concerned, 
it  would  appear  that  several  infections  may  lead  to  such 
results.  For  example,  gonorrhoea,  influenza,  puerperal  infec- 
tions, and  sometimes  rheumatic  fever.  But  apart  from 
arthritis  of  this  type,  which  can  be  traced  to  some  definite 
infection,  is  there  still  left  a  special  disease  of  bacterial  or 
non-bacterial  origin,  which  should  be  called  rheumatoid 
arthritis  ?  In  other  words,  much  the  same  problem  arises 
with  rheumatoid  arthritis  as  has  arisen  with  rheumatic  fever, 
the  problem  as  to  whether  or  not  it  is  a  specific  disease. 

Since  Max  Schiiller  first  described  micro-organisms  in  con- 
nexion with  rheumatoid  arthritis,  many  observers  have  added 
to  the  literature  ;  and  in  England  Drs.  Bannatyne,  Wohlmann, 
and  Blaxall  have  contributed  most  important  papers  to  this 
subject.     The  difficulty  which  strikes  all  who  have  followed 


CERTAIN  FORMS  OF  ARTHRITIS  155 

these  investigations  has  been  the  explanation  of  the  negative 
results  which  have  followed  experimental  inoculations.  It  is 
clearly  not  sufficient  to  inject  directly  into  the  joint  any 
micro-organisms  which  may  have  been  isolated,  for  the 
infection  in  man  does  not  take  place  in  this  direct  way.  The 
interest  of  an  investigation  we  brought  before  the  Patho- 
logical Society  of  London  early  in  this  year  lies  in  the  fact 
that  we  produced  the  lesions  of  rheumatoid  arthritis  in  rabbits 
by  intravenous  inoculation  of  a  diplococcus.  The  investiga- 
tions did  not  claim  to  demonstrate  that  the  cause  of  rheu- 
matoid arthritis  was  a  diplococcus,  for  in  the  present  state  of 
our  knowledge  of  this  disease,  and  on  the  evidence  of  a  single 
observation,  such  a  claim  would  have  been  unjustifiable, 
but  it  demonstrated  that  these  lesions  could  be  produced  by 
an  organism  injected  into  the  blood  stream,  and  not  directly 
into  the  joint,  the  lesions  including  in  addition  to  arthritic 
changes  much  wasting  of  the  muscles  of  the  limb. 

Nervous  Lesions  in  Rheumatoid  Arthritis 

Rheumatoid  arthritis  is  remarkable,  we  know,  for  the 
severity  of  the  nervous  symptoms.  They  are  so  obtrusive  as 
to  have  given  rise  to  the  widespread  belief  that  the  change  in 
the  joints  is  in  reality  a  neurotrophic  phenomenon.  But  at 
the  present  time,  although  it  is  beyond  dispute  that  the 
nervous  system  is  profoundly  affected,  there  is  considerable 
doubt  about  the  relation  that  exists  between  such  nervous 
lesions  and  the  arthritis.  Dr.  Triboulet,  in  a  paper  upon 
chronic  rheumatic  arthritis,  has  alluded  to  this  difficulty  in 
a  comment  upon  a  necropsy  he  had  made  at  the  Salpetriere 
on  a  woman,  aged  19,  who  had  died  while  suffering  from 
a  severe  chronic  arthritis  accompanied  by  extreme  muscular 
wasting.  The  spinal  cord  showed  a  system  degeneration  of 
the  posterior  columns  in  the  dorsal  region,  of  Goll's  column  in 
the  cervical,  and  a  degeneration  of  the  posterior  nerve  roots 
in  the  lumbar  region,  the  result  of  a  local  meningitis.  Dr. 
Triboulet  remarks  that,  had  not  the  history  of  this  case 
been  carefully  recorded,  it  would  have  been  easy  to  have 
explained  the  arthritis  as  secondary  to  the  meningo-medullary 
changes.  The  history,  however,  showed  that  both  the  arthritic 
and  the  neural  changes  were  the  common  result  of  a  puerperal 


156  OBSERVATIONS  UPON 

infection.  This  case  seems  to  us  to  define  the  present  position 
very  clearly,  and  we  may  state  it  in  the  form  of  this  interroga- 
tion :  Are  not  the  nervous  and  the  arthritic  phenomena  of 
rheumatoid  arthritis  the  common  result  of  some  poison  which 
has  a  special  affinity  for  these  structures  ? 


Rheumatoid  Arthritis  and  Rheumatic  Fever 

The  close  relation  of  rheumatoid  arthritis  to  rheumatic  fever 
has  certainly  been  long  recognised  by  the  medical  profession. 

Many  years  ago  Sir  Samuel  Wilks  compared  the  rheumatoid 
changes  in  rheumatic  fever  to  malignant  endocarditis  in 
rheumatic  patients.  Dr.  Herringham,  among  those  who 
joined  in  the  discussion  last  year  at  Cheltenham,  especially 
emphasised  the  close  association  of  these  two  diseases.  Per- 
haps the  most  accepted  view  about  such  cases  is  that  a 
secondary  infection  has  been  superposed  on  the  primary 
rheumatic  disease. 

We  have  demonstrated  that  the  rheumatic  organism  may 
produce  both  simple  and  malignant  endocarditis,  and  it 
appears  to  us  as  highly  probable  that  rather  than  that  a 
secondary  infection  has  been  superposed  in  such  cases,  there 
is  in  reality  an  exalted  local  virulence  of  the  original  infection. 

The  usual  clinical  history  that  precedes  malignant  rheu- 
matic endocarditis  is  one  of  repeated  simple  rheumatic  endo- 
carditis, and  with  these  forms  of  rheumatoid  arthritis  there 
may  be  also  a  previous  history  of  repeated  attacks  of  simple 
arthritis. 

It  is  a  well-established  fact  that  if  a  micro-organism  is 
injected  into  a  resistant  animal,  and  yet,  in  spite  of  this 
resistance,  succeeds  in  gaining  the  upper  hand,  the  virulence 
of  that  micro-organism  for  this  species  of  animals  is  thereby 
heightened.  This  is  a  fact  of  cardinal  importance,  and  this 
property,  inherent  to  the  infective  agent,  cannot,  we  think, 
be  overlooked.  Yet  it  is  sometimes  said,  even  by  those  who 
support  the  bacterial  origin  of  rheumatic  fever,  that  the 
disease  is  entirely  dependent  upon  the  habit  of  body,  that  the 
infective  agent  is  merely  an  excitant,  and  that  there  may  be 
more  than  one  such  infective  agent.  To  us  this  view  appears 
incomplete.  Most  certainly  the  "  soil  "  in  rheumatic  fever  is 
of   great  importance,  but  not  all-important,  and  we  are  not 


CERTAIN  FORMS  OF  ARTHRITIS  157 

at  the  present  time,  we  think,  in  a  position  to  state  how 
important. 

We  believe  it  to  be  not  improbable  that  some  cases  of 
rheumatoid  arthritis  associated  with  rheumatic  fever  are 
examples  of  this  intensification  of  bacterial  virulence.  The 
repeated  attacks  of  rheumatic  arthritis  which  precede  these 
attacks,  and  the  imperfect  recovery  from  them,  point  to  an 
infection,  quiescent  for  a  while,  but  never  conquered.  The 
local  virulence  is  raised  by  this  survival  against  the  resistance, 
and  at  length  asserts  itself.  The  type  of  the  disease  is  altered 
to  that  which,  when  it  attacks  the  heart,  is  called  malignant, 
and  the  bones  and  cartilages,  as  well  as  the  synovial  struc- 
tures, may  all  of  them  share  in  the  destructive  process.  These 
progressive  lesions,  whether  of  the  joints  or  of  the  cardiac 
valves,  appear  to  us  to  be  a  more  probable  result  of  the 
exaltation  of  the  virulence  of  the  rheumatic  infection  than 
the  development  of  a  pyaemia. 

So  far  as  one  dare  express  an  opinion  on  that  difficult 
question  of  the  relation  of  rheumatic  fever  to  pyaemia,  it  seems 
to  us  that,  though  analogous  processes,  they  are  essentially 
different  in  nature. 

Pneumococcus  Arthritis 

Arthritis  from  an  infection  with  the  pneumococcus  will  not 
detain  us  long.  To  Dr.  Cave,  we  believe,  is  due  the  credit  of 
calling  attention  to  this  condition  in  England,  and  Dr.  Nathan 
Raw  and  Dr.  G.  A.  Murray  have  also  advanced  our  knowledge 
upon  this  subject.  We  mention  it  here  to  give  further  support 
to  their  statements.  On  two  occasions  we  have  isolated  this 
organism  from  cases  of  suppurative  arthritis  complicating 
pneumonia,  and  at  the  time  we  published  our  first  results 
upon  rheumatic  fever  we  were  alive  to  the  occurrence  of 
this  form  of  arthritis,  and  did  not  fall  into  the  error  of  mis- 
taking the  pneumococcus  for  the  special  organism  which  we 
then  described. 

Suppurative  Arthritis 

The  study  of  suppurative  arthritis  brings  us  face  to  face 
with  another  difficulty  which  is  essentially  one  of  words.  The 
two  terms   "  septic  "    and   "  pus,"  though  of  great  practical 


158  OBSERVATIONS  UPON 

convenience,  are  fast  losing  their  value  in  scientific  descriptions 
of  arthritis.  They  are  suffering  much  the  same  fate  as  the 
two  other  well-known  clinical  expressions — "  hectic  "  and 
"  typhoid  state."  Just  as  these  were,  so  are  these  now,  often 
employed  to  represent  specific  conditions  when  in  reality 
they  only  represent  certain  clinical  phases.  The  pneumo- 
coccus,  for  example,  may  produce  pus,  as  also  may  the 
streptococci  and  staphylococci  ;  and  when  those  infections 
cause  severe  constitutional  symptoms,  the  condition  is  often 
called  in  each  case  septic.  Rheumatic  fever,  too,  may  perhaps, 
produce  a  pus,  yet  it  can  hardly  be  that  the  poisons  which 
produce  these  suppurations  are  in  each  case  the  same.  But 
it  is  essential  that  some  substitute  should  be  employed  for 
these  words  otherwise  we  are  left  in  a  predicament.  A  useful, 
though  incomplete,  phraseology  will  have  been  removed  and 
nothing  put  in  its  place. 

It  seems  advisable  at  the  present  time  to  use  as  a  substitute 
a  description  of  the  exudations  in  the  joints  which  is  detailed 
and  yet  which  avoids  these  two  terms,  and  in  illustration  of 
our  meaning  we  give  the  following  examples  : 

A  lad,  aged  14,  was  admitted,  under  the  care  of  Mr.  Herbert 
Page,  at  St.  Mary's  Hospital,  in  March  of  this  year  (1902), 
suffering  from  an  arthritis  of  the  left-knee-joint.  The  origin  of 
the  condition  was  obscure.  The  left  knee-joint  was  tense  with 
fluid,  the  temperature  was  raised,  and  at  times  the  boy  was 
slightly  delirious.  Ordinary  methods  of  treatment  had  been 
ineffectual,  and  Mr.  Page,  from  an  experience  of  similar  cases, 
decided  to  draw  off  the  fluid  and  wash  out  the  joint  with  a 
1  per  cent,  solution  of  carbolic  acid.  This  was  done  on  two 
occasions,  and  after  the  second  irrigation,  as  a  result  of  our 
investigation  of  the  fluid,  full  doses  of  sodium  salicylate  were 
given  in  addition.     Complete  recovery  resulted. 

Our  investigation  of  the  exudation  gave  the  following 
results  : 

1.  The  appearance  of  the  fluid  was  greenish  and  slightly 
opaque. 

2.  A  film  showed  :  (a)  Numerous  minute  diplococci,  some  in 
chains,  others  in  masses  ;  {b)  leucocytes  and  endothelial  cells, 
which  were  not  necrotic  ;    (c)  fibrin. 

3.  Culture  on  blood  agar  gave  a  pure  and  abundant  growth 
of  a  diplococcus  in  minute  discrete  colonies. 


FIG.  47 

Gonococcal  arthritis  (human  |,   Film  of  exudation,  showing1  gonococci,  mainly  intracellular. 

i  Zriss,  obj.  I1-,  oc.  3.) 


CERTAIN  FORMS  OF  ARTHRITIS  159 

4.  Intravenous  inoculation  into  rabbits  produced  multiple 
arthritis  of  all  grades  of  severity,  from  those  from  which 
recovery  was  complete  to  those  indistinguishable  from  severe 
types  of  rheumatoid  arthritis. 

It  is  clear  then  that  the  arthritis  in  this  case  was  due  to  a 
diplococcus  which  had  escaped  the  barrier  of  the  synovial 
endothelium,  had  eluded  also  the  leucocytes  in  the  exudation, 
and  was  living  free  in  the  fluid  in  a  virulent  condition.  The 
treatment  adopted  by  Mr.  Page  was  not  only  entirely  sup- 
ported by  this  investigation,  but  the  character  of  the  micro- 
organisms pointed  to  the  infection  as  of  the  rheumatic  type. 
When,  then,  the  joint  had  been  cleansed  by  the  antiseptic 
irrigation,  full  doses  of  sodium  salicylate  possibly  completed 
the  cure.  This  case  was  brought  by  Mr.  Page  and  ourselves 
before  the  Clinical  Society  of  London  earlier  in  the  year. 

Case  II.  An  infant,  aged  5  weeks,  was  brought  to  the 
Hospital  for  Sick  Children  in  Great  Ormond  Street,  in  March 
of  this  year  (1902),  with  the  following  history  :  In  the  second 
week  after  birth  the  left  ankle-joint  became  swollen  and  tender, 
then  other  joints  became  involved,  and  when  brought  to  us 
all  the  large  joints  were  affected  and  full  of  fluid.  The  bursa 
under  the  right  deltoid  was  also  tense  with  fluid.  The  natural 
explanation  appeared  to  be  either  a  septic  infection  from  the 
umbilical  cord  or  a  blenorrhagic  arthritis,  but  the  nurse,  a 
sensible  woman,  declared  the  cord  had  separated  in  a  healthy 
manner.  The  actual  cause  of  the  arthritis  must,  then,  be 
left  to  surmise.  The  condition  of  the  child  wras  one  of  extreme 
gravity,  the  more  so  as  experience  has  shown  how  often  in 
these  infants  we  have  to  deal  with  a  multiple  purulent  arthritis. 
We  took  advantage  of  the  distended  bursa  under  the  deltoid, 
and  with  precautions  drew  off  the  fluid  into  a  sterilised  pipette  ; 
even  this  slight  operation  was  followed  by  alarming  collapse, 
so  feeble  was  the  infant's  strength. 

The  examination  resulted  as  follows  : 

1.  The  fluid  was  slightly  opaque. 

2.  The  film  showed  numerous  leucocytes  which  were  not 
necrotic,  and  in  some  of  them  were  a  few  micrococci  ;  no 
micro-organisms  were  free  in  the  fluid. 

3.  Cultures  were  negatives. 

We  advised  delay  before  opening  any  of  the  joints,  and  in 
the  meantime  the  infant  was  carefully  fed  and  stimulated. 


160  OBSERVATIONS   UPON 

Complete  recovery  resulted  without  any  operation,  and  when 
the  child  was  seen  a  month  after  leaving  the  hospital  the 
recovery  was  complete.  We  believe  this  detailed  investigation 
of  the  fluid  was  a  means  of  saving  a  life. 

Case  III.  A  young  woman  was  bedridden  with  multiple 
arthritis  of  recent  origin.  She  was  unmarried,  and  no 
history  of  the  cause  could  be  obtained.  All  the  joints  re- 
covered except  the  left  ankle-joint,  which  remained  obstinate 
to  treatment  and  extremely  painful.  The  arthritis  was  so 
severe  and  the  pain  so  great  as  to  demand  exploration.  The 
surgeon,  from  the  appearance  of  the  joint  at  the  time  of 
operation,  was  inclined  to  think  the  condition  was  tuberculous. 

The  investigation  resulted  as  follows  : 

i.  The  fluid  was  blood-stained  and  yellow. 

2.  The  films  showed  numerous  gonococci,  many  within  the 
leucocytes,  but  some  also  free  in  the  fluid.  There  were 
numerous  leucocytes,  some  of  them  disintegrating. 

3.  On  culture  a  pure  and  abundant  growth  of  the  gonococcus 
on  blood  agar  was  obtained.  Experimental  investigation 
proved  negative,  which,  we  recognise  as  the  usual  rule  in 
gonococcus  infection. 

In  this  case  a  doubtful  diagnosis  was  made  clear. 

Case  IV.  A  child,  aged  18  months,  was  admitted  to  St. 
Mary's  Hospital  with  arthritis  of  both  knees.  The  skin  over 
the  joint  was  tense  and  shining,  and  the  constitutional 
symptoms  severe. 

The  result  of  the  investigation  was  as  follows  : 

1.  The  fluid  was  thick,  yellow,  and  creamy. 

2.  The  films  showed  numerous  streptococci  free  in  the 
fluid.     There  was  no  fibrin,  and  the  leucocytes  were  necrotic. 

3.  A  pure  growth  of  the  streptococcus  pyogenes  was  obtained 
on  blood  agar. 

4.  Intravenous  inoculation  into  a  rabbit  resulted  in  death 
within  twenty-four  hours  from  septicaemia. 

The  inference  from  the  investigation  was  that  this  was  a 
case  of  severe  streptococcus  pyaemia,  and  the  child  died 
within  two  days. 

We  need  not  multiply  instances  to  show  that  nothing  is 
lost  by  the  omission  of  the  terms  "  pus  "  and  "  septic  "  from 
these  descriptions,  while,  on  the  other  hand,  the  danger  of  a 
stereotyped  use  of  these  words  is  avoided. 


•  *% 


a» 


*     § 


FIG.   48 

Arthritis  (human"),  due  to  the  Streptococcus  pyogenes.    Film  of  the  exudation  showing'  the 
micro-organisms  and  cell  necrosis.     (Zeiss,  olrj.  ^,  oc.  3.) 


CERTAIN  FORMS  OF  ARTHRITIS  161 

In  conclusion,  it  is  clear  that  the  treatment  of  arthritis 
is  being  gradually  influenced,  by  the  realisation  of  the 
infective  element  in  the  causation.  We  need  only  mention 
in  support  of  this  that  Menzer,  at  Berlin,  in  June,  brought 
forward  a  specific  serum  for  articular  rheumatism.  Such 
remedies  will  be  received  with  great  caution,  but  we  must 
be  prepared  to  hear  more  of  them,  and  there  is  hope  that 
eventually  some  success  may  be  obtained  in  this  direction. 
Meanwhile  prophylactic  medicine  would  appear  to  have  a 
wide  field  before  it,  and  more  investigations  on  the  lines  of 
Dr.  Newsholme's  valuable  Milroy  lectures  can  hardly  fail  to 
be  of  interest. 

In  the  arthritic  subject  the  importance  of  the  arrest  of 
chronic  discharges  or  ulcerations,  the  careful  management  of 
the  throat,  and  the  cleansing  of  the  mouth  are  emphasised 
once  more  by  these  investigations. 

Again,*  the  realisation  of  the  two  elements,  that  of  the 
infection  and  that  of  the  resistance,  impresses  upon  us  the 
important  fact  that  no  one  method  of  treatment  can  be 
suitable  throughout  the  course  of  these  illnesses. 

Lastly,  surgical  interference,  which  has  been  so  strenuously 
advocated  from  time  to  time,  is  undoubtedly  put  on  a  surer 
basis,  though  it  is  obvious  that  the  suitable  cases  will  always 
require  careful  selection. 


11 


PART  II 

SUB-GROUP  C 

THIS  GROUP  OF  FOUR  PAPERS  WIDENS  THE  FIELD 
OF  INVESTIGATION  IN  RHEUMATISM  IN  VARIOUS 
DIRECTIONS,  AND  OPENS  UP  NEW  PROBLEMS,  SOME 
OF  WHICH  ARE  AGAIN  CONSIDERED  IN  LATER 
COMMUNICATIONS 

THE  FOLLOWING  ARE  INCLUDED  : 

XIV.  SOME  FURTHER  INVESTIGATIONS  UPON  RHEUMATIC 
FEVER 

XV.  A   CONTRIBUTION    TO   THE    STUDY   OF   MALIGNANT 
ENDOCARDITIS 

XVI.  A  CONTRIBUTION   TO   THE    STUDY    OF    RHEUMATIC 
IRITIS 

XVII.  THE  RELATION  OF  THE  STAPHYLOCOCCUS  PYO- 
GENES TO  RHEUMATIC  FEVER.  By  Dr.  F.  J.  Poynton 
and  Dr.  W.  V.  Shaw 


163 


PAPER  NO.  XIV 

SOME   FURTHER   INVESTIGATIONS   UPON 
RHEUMATIC  FEVER 

(Reprinted  from  the  Lancet,  May  1901.) 

This  paper,  published  in  1901,  has  been  taken  slightly  out  of  chrono- 
logical order  because,  with  the  other  three  in  the  first  group,  it  helped  to 
break  new  ground  in  connection  with  acute  rheumatism. 

For  the  first  time  the  true  meaning  of  the  rheumatic  nodule  was 
explained,  and  the  result  is  the  more  interesting  when  this  part  of  the 
paper  is  read  together  with  Paper  No.  VI.  The  value  of  the  method 
now  well  recognised  as  "reinforcing"  is  illustrated.  The  problem 
of  the  pathology  of  chorea  is  discussed  in  some  detail,  and  the  outcome 
of  some  further  inquiries  into  the  question  considered  and  an  explana- 
tion of  the  rheumatic  form  put  forward.  The  occurrence  of  the  diplo- 
coccus in  the  polymorphonuclear  leucocytes  is  recorded.  The  incuba- 
tion period  of  the  disease  and  the  probability  of  the  occurrence  of  fever 
as  a  primary  phenomenon  are  discussed.  The  great  importance  of  the 
production  of  morbus  cordis  is  illustrated  by  experimental  observations. 

Fritz  Meyer's  extensive  researches  upon  rheumatic  angina  faucium 
had  now  been  published,  and  in  the  main  supported  our  contentions. 
We  would,  however,  point  out,  as  Fritz  Meyer  himself  expressly  stated, 
that  he  was  unsuccessful  in  isolating  the  diplococcus  he  described, 
from  other  rheumatic  lesions. 

It  is  a  curious  fact  that  this  weak  point  in  Fritz  Meyer's  chain  of 
evidence  has  been  from  time  to  time  held  to  be  present  also  in  our 
investigations.  We  can  hardly  believe  that  those  who  have  advanced 
his  criticism  can  have  seriously  followed  our  papers. 

Since  our  first  contribution  to  this  subject,  we  have  continued 
our  investigations  and  have  now  isolated  the  diplococcus 
from  16  cases  of  rheumatic  fever.  The  particular  point  upon 
which  we  are  still  intent  is  to  establish  this  diplococcus  as 
a  cause  of  rheumatic  fever.  If  this  can  be  firmly  established 
then  the  many  difficulties  that  must  subsequently  be  faced 
can  be  dealt  with  from  a  firm  basis.     In  no  disease  perhaps 

165 


166  FURTHER  INVESTIGATIONS 

more  than  in  rheumatic  fever  is  it  necessary  to  make  this 
ground  sure,  for  it  is  in  the  centre  as  it  were  of  a  group  of 
diseases,  which  not  only  may  resemble  rheumatic  fever  closely 
in  their  clinical  features,  but  which  are  also  the  result  of 
infections  in  all  probability  closely  allied  to  that  of  rheumatic 
fever.  The  differential  study  of  the  streptococcal,  staphylo- 
coccal, gonococcal,  scarlatinal,  rheumatic,  and  probably 
rheumatoid  infections  is  one  of  great  difficulty  The  morpho- 
logical characters  of  the  various  organisms  can  only  offer  a 
partial  assistance  and  chemical  pathology  has  not  yet  ad- 
vanced sufficiently  to  render  much  service,  though  the  numerous 
researches  both  on  the  continent  and  in  this  country  into  the 
nature  of  the  toxic  processes  due  to  microbic  infections  are 
indications  of  the  importance  of  this  subject.  It  is  for  these 
reasons  that  we  have  entered  into  such  detail  in  our  efforts 
to  prove  that  this  diplococcus  is  a  cause  of  rheumatic  fever, 
and  it  is  upon  this  detail  that  we  especially  rely. 


I.    The    Isolation    of    the  Diplococcus    from    the 

Nodule 

The  first  series  of  additional  facts  that  we  are  able  to  bring 
forward  in  this  paper  is  concerned  with  the  rheumatic  nodule. 
We  have  succeeded  in  demonstrating  the  organisms  in  two 
more  nodules  and  have  in  addition  grown  them  in  the  nodular 
tissue  outside  the  body  in  pure  culture.  We  have  produced 
in  a  rabbit,  as  the  result  of  an  intravenous  inoculation  from 
this  culture  undertaken  for  us  by  Mr.  H.  G.  Plimmer,  patho- 
logist to  St.  Mary's  Hospital,  a  condition  we  believe  to  be 
that  of  acute  rheumatism — namely,  polyarthritis,  pericarditis, 
and  multiple  valvular  disease,  all  non-suppurative.  Finally, 
we  have  isolated  them  in  pure  culture  from  the  joints  of  the 
animal  after  death  and  thus  completed  the  chain  of  proof. 
And  since  these  formations  are  looked  upon  by  general  consent 
as  highly  characteristic  of  rheumatic  fever,  the  isolation  of 
this  diplococcus  from  one  of  them  will  appeal  to  many  as 
a  strong  link  in  the  proof  of  the  causal  relation  of  this  organism. 
A  short  outline  of  the  investigation  will  give  a  clearer  idea 
of  the  nature  of  this  evidence.  We  are  indebted  to  Dr. 
W.  B.  Cheadle  for  permission  to   make    use   of  the   clinical 


UPON  RHEUMATIC  FEVER  167 

notes  of  the  case,  and  to  Mr.  H.  G.  Plimmer  for  the  details  of 
the  necropsy. 

A  child,  aged  nine  years,  was  admitted  to  St.  Mary's  Hospital 
on  November  3,  1900,  suffering  from  acute  rheumatism.  When 
four  years  old  she  had  suffered  from  chorea  and  since  then 
from  three  attacks  of  acute  rheumatism.  The  present  illness 
had  commenced  four  weeks  before  admission  with  arthritis, 
and  for  three  weeks  there  had  been  shortness  of  breath.  The 
patient  was  pale  and  thin,  the  pulse-rate  was  100,  the  tempera- 
ture was  102. 4°F.,  and  the  respirations  were  40.  There  was 
dyspnoea  and  there  was  also  advanced  heart  disease.  Both 
the  mitral  and  aortic  valves  were  affected  and  the  heart  was 
dilated,  but  there  was  no  sign  of  pericarditis.  The  knees 
and  right  elbow-joint  were  painful,  but  there  was  no  effusion. 
Over  both  elbows  and  over  the  knuckles  there  were  numerous 
small  nodules.  The  urine  contained  a  trace  of  albumin.  At 
first  the  child  seemed  to  improve,  though  it  was  noted  that 
the  nodules  were  increasing  in  size.  On  November  7,  four 
days  after  admission,  a  condition  of  acute  oedema  of  the  lungs 
developed  and  proved  rapidly  fatal. 

The  necropsy  showed  recent  transparent,  bead-like  vege- 
tations upon  the  mitral,  tricuspid,  and  aortic  valves,  and  the 
mitral  and  aortic  valves  were  also  thickened  from  the  results 
of  previous  inflammation.  "  There  was  no  pericarditis,  but  there 
were  25  cubic  centimetres  of  a  straw-coloured  fluid  in  the 
pericardium.  The  lungs  were  cedematous  and  in  some  places 
there  were  haemorrhages  into  the  alveoli  and  in  others  collapse. 
The  liver  was  "  nutmegged,"  the  spleen  was  small  and  firm,  and 
both  kidneys  showed  cloudy  swelling  of  the  parenchyma  of 
the  convoluted  tubules.  Two  hours  after  death  we  removed 
three  nodules  from  the  right  elbow  with  strict  aseptic  pre- 
cautions. One  of  these  we  at  once  placed  in  the  medium 
of  milk  and  bouillon  rendered  slightly  acid  with  lactic  acid. 
The  second  we  cut  with  a  sterile  knife,  then  scraped,  and 
with  the  scraping  inoculated  a  second  tube.  The  third  we 
"  fixed  "  at  once  in  perchloride  of  mercury.  Both  tubes 
were  incubated  anaerobicahy.  The  tube  inoculated  with 
the  exudation  remained  sterile.  The  tube  containing  the 
entire  nodule  showed  no  growth  upon  the  first  day,  but  upon 
the  third  day  a  pure  culture  of  the  diplococci.  The  organisms 
were  transferred  to  blood  agar  tubes  and  grew  in  the  usual 


168  FURTHER  INVESTIGATIONS 

small,  white,  discrete  colonies.  The  contents  of  five  of  these 
tubes  were  injected  intravenously  into  a  rabbit  on  November  II. 
The  result  of  the  intravenous  inoculation  was  as  follows  :  The 
next  day  the  heart  was  very  rapid  and  there  was  a  definite 
systolic  mitral  murmur,  and  upon  the  second  day  the  hind 
limbs  were  stiff.  The  murmur  then  disappeared,  but  a  week 
after  inoculation  the  left  fore  and  hind  limbs  were  almost 
powerless,  and  in  the  next  few  days  this  weakness  and  stiff- 
ness spread  to  all  four  limbs.  A  fortnight  after  inoculation 
a  systolic  murmur  had  reappeared  and  there  was  definite 
pericarditis,  but  the  stiffness  had  disappeared  and  the  joints 
were  none  of  them  swollen.  We  were  anxious  to  obtain  a 
definite  arthritis  with  effusion,  because  we  have  found  that 
these  effusions  afford  the  easiest  and  most  reliable  local  lesions 
from  which  to  cultivate  the  organism.  Accordingly,  on 
November  26 — that  is,  the  day  after  we  had  noticed  that 
the  stiffness  had  disappeared — the  animal  was  again  inocu- 
lated with  the  organism  which  had  been  kept  growing  in  the 
acid  milk  medium.  Two  days  afterwards  stiffness  of  the 
limbs  appeared,  then  the  right  shoulder  swelled,  and  five 
days  afterwards  both  knee-joints.  The  animal  was  killed 
next  day,  and  the  post-mortem  examination  showed  mitral 
and  tricuspid  valvular  disease,  pericarditis  of  some  standing, 
and  an  opaque  fluid  in  the  right  knee-joint.  There  was  no 
suppuration  in  the  viscera.  Cultivations  were  taken  from 
the  joint  and  a  pure  growth  of  the  diplococcus  obtained. 
The  nodule  which  had  been  incubated  was  by  this  time  in 
a  pulpy  condition  from  the  effects  of  the  liquid  medium  in 
which  it  had  been  lying.  This  we  fixed  and  hardened  in 
alcohol  and  finally  embedded  and  cut  in  paraffin.  The 
nodule  that  we  fixed  in  perchloride  of  mercury  was  also 
hardened  and  cut,  and  in  the  outer  zone  we  found  some  groups 
of  the  diplococci.  It  will  be  seen  from  this  account  that  every 
circumstance  was  favourable  for  the  success  of  this  inves- 
tigation and  the  proof  a  very  conclusive  one.  In  our  previous 
papers  we  also  recorded  that  intravenous  inoculations  of  the 
diplococcus  had  produced  in  one  instance  a  nodule  over  a 
vertebral  spinous  process  and  nodular  formations  around  the 
joints  which  microscopically  resembled  the  structure  of  an 
early  nodule  in  man.  Also  that  subcutaneous  injection  of  a 
virulent  culture  had  produced  a  large  swelling  which,  slightly 


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UPON  RHEUMATIC  FEVER  169 

tender  at  first,  had  gradually  disappeared  without  any  evidence 

of  suppuration. 

This  method  of  -incubating  the  nodule  may  possibly  be 
of  some  service  to  others  who  are  interested  in  this  subject. 
We  believe  that  in  the  local  lesions  of  rheumatic  fever  the 
struggle  between  the  organisms  and  the  tissues  is  so  evenly 
balanced  that  in  many  instances  at  the  time  of  death  the 
diplococci  are  mostly  destroyed.  It,  then,  with  due  pre- 
caution, a  lesion  in  the  so-called  "  active  "  stage  be  removed 
and  incubated  in  a  suitable  medium  the  organisms  should  grow, 
for  there  is  now  no  resistance  to  prevent  their  growth-  It 
is  very  possible  that  they  do  not  regain  their  full  vitality, 
but  they  can  be  easily  demonstrated  and  may,  as  we  have 
shown,  produce  experimental  results.  Recently  we  have 
adopted  this  method  for  the  cardiac  valves,  and  instead  of 
curetting  them  have  snipped  off  the  granulaticr.s;  incubated 
them  in  the  acid  medium,  and  in  this  -  fcained  a  pure 

vth  of  diploc . 

Summary.  To  sum  up,  (1)  we  have  demonstrated  the 
diplococcus  in  three  rheumatic  nodules  taken  from  two  cases 
of  rheumatic  fever  ;  (2)  we  have  isolated  the  diplococcus  from 
the  nodule  in  one  instance  in  pure  culture  ;  (3)  intravenous 
inoculation  of  this  culture  has  produced  valvular  disease, 
pericarditis,  and  polyarthritis  in  a  rabbit ;  (4)  we  have  isolated 
the  diplococcus  from  the  joint  exudate  of  this  rabbit  ;  and 
'5;  the  nodule  is  looked  upon  as  a  highly  characteristic  mar. : 
tation  of  rheumatic  fever.  Therefore  we  conclude  that  this 
investigation  lends  strong  support  to  the  contention  that  this 
diplococcus  is  a  cause  of  rheumatic  fe 

II.     Observations  upon  the  Pathology  ob 
Rheumatig  Chorea 

In  our  paper  upon  the  ::  Path  :  0  as  .:  Rheumatic  Fever," 
read  before  the  Pathological  Society  of  London,  in  October 
1900,  we  recorded  a  condition  which  we  b  ;li  *ved  to  be  chorea 
produced  by  the  intravenous  inoculation  of  the  diplococci 
into  a  rabbit.     This  rabbit  was  extremely  :  and  in 

addition  manifested  sudden  irregular  movements  of  the  limbs 
and  face.  These  movements  were  definite,  but  not  violent, 
and  there  was  about  them  that  peculiar,  sudden,  involuntary 


i7o  FURTHER  INVESTIGATIONS 

character,  which  is  so  characteristic  of  slight  rheumatic  chorea. 
At  the  time  of  the  reading  of  this  paper  we  had  not  examined 
the  brain  further  than  to  be  able  to  state  that  there  was 
no  visible  meningitis.  Since  then  we  have  investigated  much 
of  it,  and  have  found  diplococci  in  the  pia  mater  and  in  the 
the  endothelial  cells  of  the  blood  capillaries,  dipping  into  the 
motor  cortex  from  the  surface.  The  pia  mater  in  places 
showed  some  slight  swelling  of  its  connective  tissue  and  cell 
exudation.  The  organisms  were  also  present  in  the  walls  of 
some  of  the  blood-vessels  of  the  pia  mater.  The  rabbit  which 
suffered  from  chorea,  and  also  endocarditis  and  polyarthritis, 
was  the  only  one  in  a  series  of  inoculations  from  animal  to 
animal  that  showed  these  movements.  The  others  showed 
numerous  manifestations  of  rheumatic  fever,  but  not  any 
movements  of  this  nature.  The  fatal  case  of  rheumatism, 
from  which  the  culture  was  obtained,  was  recorded  in  Paper 
VIII,  and  the  growth  was  obtained  in  the  pericardial  fluid 
itself  after  incubation.  On  another  occasion  we  isolated  the 
diplococci  from  the  cerebro-spinal  fluid  of  a  rabbit  suffering 
from  endocarditis  and  pericarditis,  but  the  animal  had  shown 
no  signs  of  chorea.  Again,  we  noted  in  a  third  rabbit  weak- 
ness of  the  hind  limbs,  which  we  suggested  might  be  paralytic 
chorea.  In  a  case  of  fatal  human  chorea  we  discovered 
micrococci  in  the  mitral  valve  and  in  the  motor  cortex,  but  the 
organisms  were  never  isolated,  and  this  observation  at  the 
best  is  not  more  than  suggestive.  Finally,  on  three  occasions, 
we  have  isolated  the  organisms  from  the  blood  in  acute 
rheumatic  pericarditis.  This  is  a  proof  in  acute  rheumatism 
with  pericarditis  that  they  may  circulate  in  the  blood  stream, 
and  therefore  presumably  in  the  cerebral  vessels  and  thus  may 
possibly  escape  to  the  cerebral  tissues. 

The  conclusion  to  which  these  observations  appear  to  lead 
is  this — that  the  commencement  of  rheumatic  chorea  is  asso- 
ciated with  the  presence  of  the  diplococci  in  the  brain  and 
perhaps  pia  mater,  as  well  as  with  the  presence  of  toxins 
produced  by  these  organisms.  If  this  be  so,  then  we  should 
be  prepared  to  find  that,  with  due  allowance  for  the  special 
anatomical  characteristics  of  the  brain,  the  morbid  changes 
produced  would  be  analogous  to  those  presented  by  other 
local  manifestations  of  rheumatic  fever.  We  can  speak  with 
confidence  of  the  nature  of  these  changes  in  the  cardiac  valves, 


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FIG.   52 

Temperature  chart  of  a   rabbit 

which      developed      choreiform 

movements  (hiring  an  attack  of 

experimental  rheumatism. 


FIG.  51 


Fig.  51.  A  section  through  the  pia  mater 
and  adjacent  brain  tissue  of  a  rabbit  that 
suffered  from  polyarthritis,  endocarditis, 
and  choreiform  movements,  the  result  of 
intravenous  inoculation  with  the  diplo- 
coccus.  Numerous  diplococci  are  seen  in  the 
pia  mater  close  to  a  large  capillary  blood- 
vessel ;  the  pia  mater  is  slightly  swollen. 


FIG.  53 

A  capillary  blood-vessel  in  the  motor  cortex  of  the  rabbit's  brain— see  preceding- 
figure — showing  diplococci  in  tbe  endothelial  cells 


UPON  RHEUMATIC  FEVER  171 

myocardium,  pericardium,  and  nodules.  If  the  process  is  acute 
the  connective  tissues  swell ;  there  is  hyaline  degeneration, 
and  there  may  be  necrosis.  Where  there  are  blood-vessels 
there  is  hyperaemia,  and  there  may  even  be  small  haemorrhages 
and  thromboses.  There  is  also  fibrino-cellular  exudation. 
The  cardiac  muscle  fibres  lose  their  striation  and  there  may 
be  well-marked  fatty  changes.  There  is  connective  tissue  cell 
proliferation,  and  if  the  process  has  been  severe  and  of  long 
duration  there  is  sclerosis  spreading  from  the  position  of  the 
small  blood-vessels.  Then  we  also  know  that  the  diplococci 
in  the  valves,  pericardium,  and  nodules,  are  rapidly  destroyed 
at  the  sites  of  the  lesions,  though  it  is  probable  that  the  poisons 
that  are  produced  may  linger  after  the  disappearance  of  the 
organisms.  But  we  are  in  ignorance  as  to  the  nature  of 
any  poisons  that  may  be  formed  by  the  action  of  the  diplococci. 

If  these  observations  are  applied  to  the  pathology  of  rheu- 
matic chorea,  we  should  expect  to  find  that  the  lesions  in 
chorea  are  various.  In  very  acute  and  rapidly  fatal  cases  we 
should  expect  hyperaemia,  possibly  small  haemorrhages,  and 
foci  of  necrosis  in  the  cerebral  tissues  ;  also  minute  emboli 
or  thromboses  in  the  terminal  capillaries.  In  the  less  acute 
cases  we  should  expect  changes  in  the  region  of  the  minute 
blood  capillaries,  such  as  cell  exudation  and  cell  proliferation, 
and  also  degeneration  of  nerve  cells.  In  the  chronic  cases  we 
should  expect  perivascular  fibrosis  and  small  areas  of  sclerosis. 
There  would  probably  be  considerable  difficulty  in  demonstrat- 
ing the  organisms,  especially  in  the  more  chronic  cases.  On  the 
other  hand,  it  is  quite  possible  in  some  cases  that  they  may 
be  present  in  such  numbers  that,  escaping  from  the  vessels  into 
the  brain  tissue,  they  may  set  up  sufficient  swelling  in  the 
neighbourhood  of  these  minute  capillaries  to  cause  their 
occlusion  from  pressure  upon  the  delicate  walls.  On  the 
other  hand,  our  investigations  throw  no  light  upon  the  regional 
localisation  of  chorea,  neither  do  they  throw  fight  upon  the 
action  of  toxins  or  the  characteristics  of  the  brain  itself,  both 
most  important  factors  in  the  pathology  of  chorea.  It  would, 
however,  appear  probable  that  the  actual  commencement  of 
chorea  in  rheumatism  is  associated  with  the  presence  of  the 
diplococci  in  the  brain. 

Up  to  this  point  we  have  contented  ourselves  with  reasoning 
from  our  facts  upon  the  pathology  of  chorea.     It  now  remains 


:-:  FURTHER  INVESTIGATIONS 

for  us  to  allude  to  some  of  the  numerous  observations  of  other 
■-• .   stigators  upon  this  subject,  which  have,  it  is  clear,  guided 
conclusi  1  which  are  of  the  utmost 

importance  in  a:  :igation  of  such  a  nature  as  this  one. 

In  1863  Dr.  Kirkcs,1  noticing  the  constant  presence  of  vegeta- 
tions on  the  valves  of  the  heart  in  fatal  chorea,  suggested  that 
the  disease  might  be  caused  by  the  irritation  produced  in  the 
-  centres  by  fine  molecular  particles  of  fibrin,  which  were 
-  t  ::  from  the  inflamed  endocardium  and  carried  by  the 
blood  into  the  capillaries  of  those  cavities.  Dr.  Hughlings 
Jackson,2,  3  in  1864,  wrote  :  "  I  think  from  mam'  circumstances 
that  embolism  is  a  frequent  cause  of  chorea.  I  do  not  say 
plugging  of  the  trunk  of  the  middle  cerebral,  but  probably  of 
some  of  its  ram-  :ich  supply  com  is  near  to  the 

corp  stii  torn-"  In  1S65  Sir  William  Broadbent,4  by  an  in- 
dependent research,  arrived  at  much  the  same  conclusion  as 
had  Dr.  Hughlings  Jackson,  and  also  laid  stress  upon  the 
importance  of  ah  -  in  the  blood  as  a  predisposing  cause. 

Dr.  H.  M.  Tuckwell,5  in  1867,  published  a  case  of  chorea  in 
which  the  necropsy  disclosed  an    .  superficial  softening 

of  the  convolutions,  th  mbolism.     And  again,  in 

th     St.  1  s  Hospital  Reports  for  1869,  he  recorded 

another  fatal  case  in  which  ther  mbolism  of  the  right 

post  :  rebial   artery,  and  figured  in  a   plate   both  the 

mitral  valve  and  the  v  -  1  that  had  been  plugged.  It  is 
impossible  tc  r-  -  turn  t  ilue   of  those  rches, 

for  they  at  once  brought  the  subject  into  the  field  of 
contr  rsy  ind  put  forward  a  hypothesis  capable  of  proof 
or  disproof. 

The  wh  I     _     -don  of  cerebral  diseL-  irther  advanced 

.imental  researches  of  Fitz,  Hitzig,  Ferrier,  and 

is  upon  cerebral  localisation.    Later  opponents  arose  to  the 

embolic  theory,  Ogle,  Barnes,  Dickinson,  Bristowe,  and  Bastian 

in  particular  advancing  obj  to  this  hypothesis.     Dr. 

W.  H.  Dick::  :    "      wrote  thus  upon  this  question  : 

see  in  chcr  i  iely  distributed  by-peraemia    of    the 

nervous  centres,  not  due  to  any  mechanical  mischance,  but 
produced  by  causes  mainly  of  two  kinds — one  a  morbid, 
probably  humoral  influence  which  may  affect  the   nervous 

-    as  it  af:      -      ther  organs  and  tissues;    the   other, 
irritation  in  some  mode,  usually  mental,  but  sometimes  what 


UPON  RHEUMATIC  FEVER  173 

is  called  reflex,  which  especially  belongs  to,  and  disturbs,  the 
nervous  system,  and  affects  persons  differently,  according  to 
the  inherent  mobility  of  their  nature.  The  course  of  the 
disease  is  sufficiently  traced  in  hyperaemia  and  its  results." 
Dr.  H.  C.  Bastian,7  in  1877,  in  a  paper  entitled,  "  Remarks 
on  the  Pathology  of  Chorea,"  writes  :  "  In  common  with  many 
who  have  spoken  with  greatest  authority  on  this  subject,  I 
look  (certain  rare  cases  excepted)  to  an  altered  and  often 
anaemic  blood  state  as  its  predisposing  cause  in  individuals 
of  a  certain  age  and  nervous  temperament.  Secondly,  I  look 
to  the  irritation  in  such  individuals  of  a  disturbed  nutrition 
in  the  corpora  striata  and  adjacent  parts  of  the  brain,  tending 
to  issue  and  often  actually  issuing,  in  what,  for  want  of  any 
more  appropriate  term,  may  be  called  a  subacute  inflam- 
mation of  these  centres — often  characterised  in  part  by  the 
production  of  multiple  minute  thromboses."  In  1876  Dr. 
Hughlings  Jackson,  after  alluding  to  those  cases  of  chorea 
in  which  Dr.  Bastian  found  plugging  due  to  thrombosis,  writes  : 
"  It  may  be,  I  would  admit  here,  that  the  hypothesis  of 
embolism  will  be  displaced  by  Bastian's  hypothesis  of  throm- 
bosis as  an  explanation  of  many  cases  of  chorea."  In  a  foot- 
note to  this  paper  he  further  writes  :  "  Having  regard  to  the 
great  elaborateness  of  the  movements  in  chorea,  I  still  think  it 
most  probable  that  the  convolutions  are  the  parts  diseased." 
Since  the  time  of  those  papers  numerous  investigators  in 
England  and  on  the  continent  have  proved  beyond  controversy 
that  chorea  and  rheumatic  fever  are  very  frequently  associated, 
so  frequently,  indeed,  that  some  have  thought  that  all  chorea 
was  the  result  in  some  way  or  another  of  rheumatism.  As 
this  association  became  certain,  it  was  natural  that  the  view 
that  some  poison  (the  result  of  the  rheumatic  state)  was  the 
actual  cause  of  chorea  should  gain  many  adherents.  A  con- 
siderable amount  of  information  has  also  been  gained  about 
the  morbid  anatomy  of  fatal  chorea,  though,  as  pointed  out 
by  Dr.  Risien  Russell8  in  his  article  upon  Chorea  in  Professor 
Clifford  Allbutt's  "  System,"  many  of  these  investigations 
have  not  been  sufficiently  thorough.  It  is  easy  to  understand 
the  difficulty  of  such  investigations  when  it  is  borne  in  mind 
that  those  who  have  undertaken  them  had  but  little  to  guide 
them  as  to  what  to  look  for,  or  where,  in  such  a  large  organ  as 
the  brain,  to  look.     It  would  appear  nevertheless,  that  the  more 


174  FURTHER  INVESTIGATIONS 

careful  the  researches  the  more  frequently  have  some  definite 
morbid  changes  been  discovered.9  Hyperaemia  appears  to  be 
common,  as  also  softening  from  the  effects  of  minute  emboli.10 
Punctiform  haemorrhage  and  perivascular  exudations  have 
also  been  found.11  The  late  Dr.  Charlewood  Turner12  described 
cloudy  swelling  of  the  large  pyramidal  cells,  and  Dana13 
hyaline  swelling  of  nerve  cells  and  chronic  lepto-meningitis. 

Another  result  of  the  establishment  of  the  association  of 
rheumatic  fever  and  chorea  was  the  view  that  the  changes 
in  the  brain  were  analogous  to  those  which  occur  in  the  valves 
of  the  heart  and  in  the  subcutaneous  nodules.  To  quote 
from  the  Harveian  Lectures  for  1888,  by  Dr.  W.  B.  Cheadle  : 14 
"  I  may  point  to  the  possibility  of  some  proliferative  change 
in  the  neuroglia  akin  to  that  of  the  fibrous  tissue  elsewhere  as 
a  point  which  needs  examination."  If  these  local  lesions  in 
rheumatic  fever  be  each  one  of  them  looked  upon  as  an  indivi- 
dual and  complete  rheumatic  process,  then  we  have  the  clinical 
expression  of  such  a  view  as  the  above  in  the  statement  by  Sir 
Dyce  Duckworth,16  that  chorea  is  cerebral  rheumatism,  in 
support  of  which,  in  1894,  he  read  a  paper  in  Rome  at  the 
International  Congress  of  Medicine.  Again,  in  a  recent 
communication  to  us,  Dr.  Hughlings  Jackson  refers  to  the 
possibility  that  some  of  the  changes  in  the  brain  are  analogous 
to  those  found  in  the  cardiac  valves  and  subcutaneous  nodules. 
On  the  other  hand,  the  view  that  chorea  was  in  most  part  the 
direct  effect  of  rheumatic  fever  was  opposed  by  such  an 
authority  as  Sir  William  Gowers,16  in  his  "  Manual  of  Diseases 
of  the  Nervous  System,"  in  1893.  He  admitted  the  frequency 
of  association  of  the  two,  but  writes  :  "  The  hypothesis 
which  seems  best  to  explain  the  facts  is  the  old  theory  that  the 
common  cause  of  the  endocarditis  and  the  chorea  is  a  blood 
state  allied  to,  but  not  identical  with,  that  which  causes  acute 
rheumatism."  He  considered  that  the  facts  suggested  a 
toxic  change  of  a  chemical  character  rather  than  an  organised 
virus. 

One  of  the  most  recent  researches  upon  the  morbid  anatomy 
of  acute  chorea  is  that  of  Dr.  Bertram  Abrahams.17  The 
patient,  aged  28,  was  pregnant  ;  there  was  a  history  of  scarlet 
fever  but  not  of  rheumatic  fever,  and  during  life  there  was  a 
systolic  mitral  murmur  pointing  to  slight  mitral  endocarditis 
The  illness  lasted  from  April  25,  1899,  to  June  1.     The  moto 


UPON  RHEUMATIC  FEVER  175 

cortex  showed  changes,  especially  upon  the  right  side  in  the 
region  of  the  right  parietal  lobe.  In  this  region  there  was 
a  profuse  exudation  of  small  cells  which  were  found  to  be 
uninuclear  leucocytes.  In  some  sections  these  cells  could  be 
traced  passing  through  the  walls  of  the  small  blood-vessels 
and  outside  the  vessels  occupied  the  peri-neuronal  lymph 
spaces.  There  were  haziness  and  swelling  of  the  pyramidal 
cells.  There  was  no  trace  of  micro-organisms.  Dr.  Abrahams, 
in  his  comments,  writes  as  follows  :  "I  would  venture,  how- 
ever, to  submit  that  it  tends  to  support  the  following  general 
deductions.  Firstly,  the  changes  noted  are  sufficient  to 
explain  the  clinical  manifestations  of  the  disease  on  the  ground 
of  disturbances  in  the  cells  of  the  so-called  motor  cortex. 
Sscondly,  their  nature  is  such  as  to  be  susceptible  of  complete 
and  rapid  recovery — a  fact  in  harmony  with  the  description 
of  the  disease  as  functional.  Thirdly,  there  is  nothing  in  them 
inconsistent  with  the  conception  of  chorea  as  an  affection 
produced  by  a  blood  state — namely,  the  rheumatic  toxaemia." 
With  the  development  of  bacteriology  new  facts  were  obtained, 
and  during  the  last  fifteen  years  the  opinion  that  rheumatic 
fever  was  of  microbic  origin  has  steadily  gained  ground.  This 
resulted  in  the  recognition  of  the  possibility  that  some  bacterial 
poison  might  be  the  cause  of  rheumatic  chorea,  an  idea 
strengthened  by  the  analogy  of  the  occurrence  of  diphtheritic 
paralysis  as  a  result  of  the  infection  with  the  specific  bacillus 
of  diphtheria.  But  though  the  view  that  the  condition  might 
be  the  result  of  some  poison  circulating  in  the  blood  gained 
in  force,  there  still,  we  believe,  must  be  recognised  the  clinical 
fact  that  rheumatic  chorea  is  often  remarkably  asymmetrical 
in  its  distribution,  sometimes  focal,  and  this,  we  think,  mihtates 
against  the  theory  of  a  diffuse  poison  being  the  only  causal  agent, 
and  points  rather  to  multiple  local  lesions  being  present  in 
addition  to  the  more  diffuse  cerebral  toxaemia. 

Finally,  within  the  last  ten  years,  various  observers  have 
isolated  organisms  from  the  brain  and  its  pia  mater  in  fatal 
chorea.  The  organisms  most  usually  found  have  been  cocci,18 
though  Pianese,19  in  1893,  isolated  a  bacillus  which  produced 
convulsions  in  animals.  In  1894,  Dana20  isolated  a  diplo- 
coccus  from  the  meninges,  and  in  1898,  Apert21  isolated  a 
diplococcus  from  the  brain,  and  was  of  opinion  that  the 
organism  was  similar  to  that  described  bv  Triboulet22  as  a 


i76  FURTHER  INVESTIGATIONS 

cause  of  aggravated  rheumatic  fever.  In  1899  Westphal 
Wassermann  and  Malkoff23  isolated  from  the  brain  in  a  fatal 
case  of  chorea  a  diplococcus  which  produced  fever  and  multiple 
arthritis  in  a  series  of  eighty  rabbits.  This  diplococcus  Pro- 
fessor Wassermann  considered  to  be  the  specific  cause  of 
rheumatic  fever.  In  1899,  Maragliano,24  as  a  result  of  his 
researches,  considered  chorea  to  be  a  cerebral  infection  by 
staphylococci,  and  maintained  that  the  disease  was  due  either 
to  the  presence  of  these  organisms  or  to  the  poisons  which 
they  produced.  In  1900  we  produced  chorea  in  a  rabbit  by 
the  intravenous  inoculation  of  a  diplococcus,  which  we  believe 
to  be  a  cause  of  rheumatic  fever,25  and  demonstrated  the 
organisms  in  the  pia  mater  and  in  the  endothelial  cells  of  the 
blood  capillaries  dipping  into  the  cortex. 

It  remains  for  us  to  consider  some  of  the  clinical  charac- 
teristics of  rheumatic  chorea  and  to  attempt  to  explain  them 
by  the  hypothesis  that  in  most  cases,  possibly  all,  the 
commencement  of  the  disease  is  the  result  of  the  actual 
presence  of  the  diplococci,  together  with  the  poisons  they 
produce  in  the  brain.  Any  such  considerations  must  be 
limited  by  our  ignorance  of  the  part  taken  in  the  disease  by 
the  brain  itself,  which  fact  is  without  doubt  a  very  important 
one,  and  also  by  our  ignorance  of  the  exact  action  of  the 
toxins  that  are  produced  by  the  organisms.  The  hypothesis 
involves  the  consideration  of  two  morbid  processes  in  the  actual 
production  of  the  disease — one,  focal  dependent  upon  the  tissue 
changes  in  the  regions  where  the  diplococci  are  located,  the 
other  dependent  upon  the  toxic  effects  of  the  poisons  upon 
the  nerve  elements.  How  much  is  to  be  attributed  to  each 
factor  will  be  made  far  more  clear  when  these  poisons  can  be 
isolated  and  studied  by  experiment. 

The  onset  of  chorea  is  usually  gradual,  some  times  acute, 
in  rare  cases  almost  sudden.  In  the  acute  cases  it  is  reasonable 
to  suppose  that  there  is  a  considerable  and  rapid  invasion  of  the 
brain  by  diplococci.  It  is  possible  that  they  escape  from 
the  vessels  and  set  up  swelling  and  exudation  in  the  surrounding 
tissues,  just  as  in  the  nodule  they  may  rapidly  give  rise  to  a 
swelling  which  is  perceptible  to  the  eye.  In  cases  of  more 
gradual  onset  the  invasion  is  probably  less  severe  either  in 
the  intensity  of  virulence,  or  in  the  number  of  the  organisms 
that  gain  access  to  the  brain.     The  symptoms  are  sometimes 


UPON  RHEUMATIC  FEVER  177 

focal  and  sometimes  general,  and  are  dependent  upon  the 
factors  mentioned  above.  The  lesions  that  are  produced 
usually  resemble  those  represented  by  the  nodules  in  the 
completeness  of  their  recovery  and  also  in  their  varying  dura- 
tion. This  analogy  must,  however,  not  be  pushed  too  far. 
We  recognise  that  the  cerebral  processes  are  peculiar,  for 
they  are  of  such  complexity  that  when  disordered  they  are 
especially  slow  to  return  to  normal,  even  though  the  actual 
cause  of  the  disturbance  may  have  been  removed.  Some 
rare  cases  are  fatal,  the  intensity  of  the  disease  resembling 
then  the  severe  types  of  rheumatic  carditis.  Other  cases 
recover  only  partially,  and  for  years  a  chronic  condition  of 
disordered  movement  persists.  We  should  suspect  that  this 
points  to  some  actual,  though  slight,  multiple  organic  lesions, 
and  in  such  cases,  also,  some  peculiarity  in  the  brain  itself 
is  highly  probable.  This  view  is  supported  by  the  patho- 
logical changes  that  have  been  found  in  that  chronic  pro- 
gressive form  of  chorea  known,  as  Huntingdon's  chorea.  It 
was  clearly  demonstrated  by  the  earliest  investigators  that 
the  paralytic  manifestations  are  the  result  of  a  more  severe 
nerve  lesion  than  are  the  inco-ordinate  movements.  These 
paralytic  symptoms  we  would  associate  with  local  tissue 
changes  in  the  regions  invaded  by  the  diplococci. 

That  only  certain  cases  should  develop  chorea  is  remarkable 
and  cannot  as  yet  be  explained,  but  it  is  only  a  further  evidence 
of  the  specific  action  of  the  more  complex  poisons,  the  truth 
of  which  we  have  been  led  to  recognise  by  the  study  of  peri- 
pheral neuritis.  There  is  little  doubt,  too,  that  in  children 
more  cases  than  are  perhaps  generally  recognised  present 
slight  manifestations  of  chorea  during  acute  rheumatism 
(a  point  which  has  been  emphasised  by  Sir  Thomas  Barlow). 
Again,  many  others,  without  evidence  of  actual  chorea,  are 
highly  nervous  and  excitable  during  an  attack  of  rheumatic 
fever.  That  the  disease  should  be  common  in  children  and 
rare  in  adults  is  in  accord  with  many  other  acute  infections  ; 
the  child  is  less  resistant  to  them  than  the  adult,  and  the 
manifestations  are  more  widespread. 

The  causal  relation  of  fright  to  chorea  is,  and  always  has 
been,  a  great  difficulty.  Some  authorities — for  example, 
the  late  Dr.  Sturges26 — have  attributed  to  fright  and  mental 
strain  a  most  important  position,  others  with  equal  ability 

12 


178  FURTHER  INVESTIGATIONS 

have  opposed  this  view.  The  truth  probably  lies  in  the  middle 
course.  Many  of  the  examples  attributed  to  fright  have,  no 
doubt,  only  proved  that  the  condition  of  the  brain  must  have 
been  very  unstable,  and  the  essential  point  has  been,  not  the 
trivial  cause  of  a  fright,  but  this  condition  of  instability.  It 
is  well  known  that  rheumatic  children  are  often  highly  nervous 
and  excitable,  and  especially  so  before  an  attack  of  chorea  ; 
this  fact  has  been  insisted  upon,  among  others,  by  Dr.  J.  F. 
Goodhart,  Dr.  W.  B.  Cheadle,  and  Sir  Dyce  Duckworth,  and 
quite  recently  by  Dr.  G.  F.  Still.  How  much  of  this  instability 
in  any  case  of  chorea  is  to  be  attributed  to  hereditary  weak- 
ness and  how  much  to  latent  rheumatic  processes  it  is  difficult 
to  decide.  At  present  the  pathological  processes  that  result 
from  fright  are  unknown,  though  on  the  clinical  side  it  is 
recognised  that  their  effects  may  be  as  far  reaching  and  of  as 
long  duration  as  morbid  conditions  produced  by  bacterial 
poisons.  The  association  of  fright  and  rheumatic  chorea 
appears  to  stand  at  present  thus.  Rheumatism  produces  a 
cerebral  state  analogous  to  that  produced  by  fright  ;  what 
that  condition  is  we  do  not  know.  When  chorea  arises  in  a 
rheumatic  child  and  is  attributed  to  fright,  it  would  seem 
probable  that  the  fright  acted  upon  the  rheumatic  brain  much 
as  strain  acts  upon  the  rheumatic  heart — namely,  intensified 
the  rheumatic  process  in  the  brain  and  precipitated  chorea, 
as  does  strain  hasten  the  onset  of  rheumatic  carditis.  Such 
a  brain  previous  to  the  fright  is  unstable  from  rheumatic  in- 
fection, and  then  the  fright  itself  lowering  still  more  the  cere- 
bral resistance,  starts  some  times  at  once,  sometimes  after 
a  short  interval,  the  actual  phenomena  of  chorea. 


III.    The  Occurrence  of  the  Diplococci  in  the 
Polymorphonuclear  Leucocytes 

By  centrifugalising  the  pericardial  exudate  from  a  case 
of  acute  rheumatic  pericarditis,  we  have  succeeded  in  demon- 
strating the  presence  of  these  organisms  in  the  polymor- 
phonuclear leucocytes.  In  one  instance  there  were  as  many 
as  three  pairs  of  diplococci  in  one  leucocyte.  In  rabbits  we 
have  also  demonstrated  them  in  the  same  cells  in  the  joint 
exudate.     The  fact  that  the  diplococcus  can  be  discovered  in 


UPON  RHEUMATIC  FEVER  179 

the  polymorphonuclear  leucocytes  is  of  interest  because  it  is 
well  known  that  there  is  a  moderate  leucocytosis  in  rheumatic 
fever.  It  is  therefore  possible  that  this  leucocytosis  is  pro- 
tective in  function. 


IV.    The  Incubation  Period  of  Rheumatic  Fever 

It  does  not  seem  very  probable  from  our  observations  that 
rheumatic  fever  has  a  definite  incubation  period.  If  it  should 
so  happen  that  a  very  considerable  infection  suddenly  occurred, 
then  the  symptoms  show  themselves  rapidly.  Dr.  A.  E. 
Garrod27  in  his  treatise  gives  several  examples  in  which  the 
local  symptoms  showed  themselves  on  the  second  day  or  within 
the  first  week,  and  in  these  instances  there  was  a  very  definite 
history  of  chill  and  cold.  Rabbits  intravenously  inoculated 
usually  show  the  first  local  lesions  at  the  end  of  the  second  or 
the  beginning  of  the  third  day.  On  the  other  hand,  the 
resistance  to  the  disease  being  great,  it  may  well  be  in  other 
instances  that  for  some  considerable  time  the  infection  is 
kept  at  bay  and  general  indeterminate  symptoms  alone  be 
manifested.  Then  one  of  two  events  may  occur  :  either  the 
resistance  may  prove  effectual  and  the  illness  come  to  an 
end  without  having  ever  been  recognised  as  rheumatic  fever, 
or  the  infection  may  conquer  and  rheumatic  fever  result  after 
a  considerable  period  of  previous  ill-health.  This  occurrence 
of  rheumatic  fever  after  some  weeks  of  previous  malaise  is 
thoroughly  recognised  by  clinicians. 

In  the  consideration  of  this  question  a  study  of  the  tonsils 
after  death  is  of  some  interest.  These  are  not  uncommonly 
enlarged  and  very  unhealthy  at  the  time  of  death,  and  when 
sections  are  made  through  them  scattered  foci  of  inflammatory 
exudation  may  be  discovered  at  some  distance  from  the  surface 
(a  point  insisted  upon  by  Dr.  William  Hill28  in  1889),  the 
structure  of  the  tonsil  itself  is  indurated  and  points  to  a  con- 
dition of  subacute  inflammation  and  disease  of  long  standing. 
In  such  a  condition  as  this  we  naturally  wonder  how  great 
possibilities  for  harm  exist  in  these  scattered  foci  of  active 
disease,  to  what  extent  the  organisms  may  develop  at  these 
sites,  and  to  what  extent  they  may  gain  access  to  the  system. 
The  importance  of  this  question  has  been  still  more  accentuated 


i8o  FURTHER  INVESTIGATIONS 

by  the  extensive  researches  of  Fritz  Meyer,29  conducted  in 
the  laboratory  of  Professor  von  Lcyden,  and  published  in 
February  1901.  Meyer,  after  an  investigation  extending 
over  two  years,  succeeded  in  repeatedly  isolating  from  the 
throat  in  rheumatic  patients  a  diplococcus  easily  discolourised 
by  Gram's  method.  This  grew  well  on  blood  agar  in  staphy- 
lococcal masses,  and  in  liquid  media  of  high  alkalescence 
in  streptococcal  chains,  and  produced  in  rabbits  the  same 
phenomena  as  did  the  diplococcus  isolated  by  ourselves. 


V.     Is    Fever    a    Primary    Phenomenon    in    Rheumatic 
Fever,  or  is  it  Secondary  to  the  occurrence  of  Local 

Lesions  ? 

Upon  this  point  we  are  able  to  bring  forward  some  facts 
which  suggest  that  fever  may  be  a  primary  phenemenon  of 
the  disease.  This  view  has  been  held  by  such  authorities 
as  Graves,  Todd,  Fuller,  and  others,  while  on  the  other  hand, 
Besnier  and  Homolle  considered  the  fever  to  be  secondary 
to  the  local  lesions.  In  the  valuable  monograph  by  Dr.  A. 
E.  Garrod  upon  rheumatism  the  evidence  for  and  against 
these  views  and  the  difficulty  there  is  in  arriving  at  a  solution 
of  this  question  are  stated  with  great  clearness.  As  Dr.  Garrod 
has  written,  "It  is  only  from  the  presence  of  the  local  mani- 
festations that  it  is  possible  to  be  sure  of  the  nature  of  the 
attack."  Experiment  overcomes  this  difficulty  in  some 
measure,  but  at  present  not  altogether,  for  we  do  not  under- 
stand exactly  the  method  of  infection  in  rheumatic  fever. 
Granting,  for  example,  that  the  throat  is  an  important  site  of 
infection,  we  cannot  say  precisely  under  what  conditions  the 
diplococci  gain  access  to  the  system,  though  it  is  probable  that 
the  path  is  through  the  lymph  channels. 

The  experimental  method  of  intravenous  inoculation  is 
a  gross  method,  for  one  considerable  dose  of  the  organisms 
is  at  once  injected  into  the  circulatory  system  and  all  re- 
sistance at  the  site  of  inoculation  put  out  of  court.  Admitting 
this,  it  is  clear  that  we  can  by  this  means  state  precisely  when 
infection  took  place,  and  therefore  can  judge  whether  fever 
is  a  primary  phenomenon  or  not  under  those  conditions.  We 
have  found  the  temperature  rise  within  twenty-four  hours, 
whereas  the  local  lesions  usually  do  not  appear  until  the  third 


UPON  RHEUMATIC  FEVER  181 

day.  In  one  case  pericardial  fluid  from  a  case  of  rheumatic 
pericarditis  was  removed  in  sterilised  pipettes  four  hours  after 
death,  and  then  incubated  for  twenty-four  hours.  The 
fluid  contained  the  diplococci  in  great  numbers.  This  was 
intravenously  inoculated,  and  four  hours  afterwards  the 
temperature  had  risen  to  105 ° — a  more  pronounced  rise  of 
temperature  than  occurred  when  cultures  upon  blood  agar 
were  used.  This  result  suggests  that  toxins  in  the  pericardial 
fluid  might  have  assisted  in  causing  this  rapid  rise  of 
temperature. 

VI.    The  Experimental  Production  of  Morbus 
Cordis 

Whatever  views  may  be  held  by  others  regarding  the  relation 
of  this  organism  to  rheumatic  fever,  there  can  be  no  possible 
doubt  that  it  is  capable  of  producing  cardiac  lesions  with 
great  constancy.  We  have  repeatedly  observed  the  occurrence. 
The  mitral,  tricuspid,  and  aortic  valves  have  all  been  affected, 
and,  in  addition,  dilatation  of  the  heart  with  fatty  change 
in  the  myocardium  and  pericarditis  has  occurred.  These 
results  are  extremely  suggestive  of  the  true  meaning  of  the 
infection.  It  seems  highly  probable,  too,  that  the  study  of 
heart  disease  may  be  simplified  and  be  made  more  certain 
by  observations  upon  the  conditions  experimentally  produced. 
There  is  one  aspect  of  this  subject  which  has  a  very  important 
bearing  upon  the  study  of  rheumatism,  and  that  is  the  in- 
volvement of  the  right  side  of  the  heart.  It  is  repeatedly 
stated  that  the  right  side  of  the  heart  is  but  rarely  affected 
in  rheumatic  fever,  and  so  frequently  is  this  statement  made 
that  we  believe  it  may  lead  to  error.  Sir  Thomas  Barlow, 
among  others,  has,  to  our  knowledge,  frequently  pointed  out 
that  several  valves  are  usually  injured  in  the  severe  rheumatic 
carditis  of  childhood,  and  in  such  cases  we  believe,  with  others, 
that  it  is  comparatively  common  for  the  tricuspid  valve  to  be 
affected.  The  lesions  are  less  severe,  no  doubt,  often  indeed 
very  slight,  but  they  are  frequently  present.  Again,  when  it  is 
remembered  that  the  tendency  of  these  lesions  in  rheumatism 
is  towards  recovery,  it  may  well  be  that  a  thickening  of  the 
tricuspid  segments,  in  reality  of  previous  rheumatic  origin, 
may  be  ascribed  entirely,  rather  than  in  part,  to  mechanical 


182  FURTHER  INVESTIGATIONS 

overstrain  the  result  of  some  advanced  lesion  upon  the  left 
side.  The  question,  as  it  presents  itself  in  rheumatic  fever, 
is  one  of  degree,  and  to  argue  that  an  affection  of  the  right 
side  of  the  heart,  even  if  severe,  cannot  be  rheumatic,  but 
is  due  to  a  secondary  infection,  is,  we  believe,  to  assume 
more  than  can  be  granted.  When  the  extremely  delicate 
valves  of  the  rabbit's  heart  are  affected,  the  granulations 
are  minute  and  the  distinction  between  the  affection  of  the 
valves  on  the  right  and  on  the  left  side  less  evident.  The 
aortic  segment  of  the  mitral  is,  however,  as  in  man  a  less 
delicate  structure,  and  it  is  in  that  segment  that  we  have 
noted  in  addition  to  granulations  some  thickening  and  opacity. 
It  is  possible,  therefore,  that  the  preponderance  of  the  mitral 
disease  in  rheumatism  is  in  part  dependent  upon  the  more 
elaborate  structure  of  that  valve.  It  is  quite  possible  that  by 
the  experimental  method  the  solution  of  certain  other  diffi- 
culties will  be  obtained,  for  just  as  in  man  the  mitral  valves  or 
the  aortic  may  be  apparently  alone  affected,  so  in  rabbits  we 
have  observed  the  same  occurrence  ;  yet  even  in  those  cases 
in  which  only  one  valve  apparently  is  affected  it  is  quite 
possible  that  more  than  one  was  infected,  but  that  these  others 
have  by  virtue  of  the  phagocytic  action  of  their  connective 
tissue-cells,  destroyed  the  invading  organisms  which  attacked 
them  in  comparatively  small  numbers. 

At  the  risk  of  repetition  we  would  once  more  state  that 
injury  to  the  tricuspid  valve  in  the  severe  rheumatic  carditis 
of  childhood,  though  slight  in  extent,  is  frequent  in  its  occur- 
rence, and  the  more  carefully  it  is  looked  for  the  more  fre- 
quently it  will  be  found  to  occur.  That,  if  rheumatic  fever 
is  a  disease  due  to  an  infection,  there  is  danger  in  the  assump- 
tion that  disease  of  the  tricuspid  valve  in  a  rheumatic  patient  is 
necessarily  due  to  a  secondary  infection.  That  such  may  be 
the  case  is  certain,  but  how  often  it  is  the  case  yet  remains  to 
be  proved.  Again,  when  a  patient  who  has  been  the  victim 
of  repeated  rheumatic  attacks  dies  from  malignant  endo- 
carditis, it  is  quite  as  legitimate  to  assume  that  the  condition 
is  truly  rheumatic,  though  altered  in  type,  as  it  is  to  assume 
the  occurrence  of  some  secondary  infection.  If  the  organisms 
are  isolated  from  the  valve  and  demonstrated  as  specific  yet 
not  rheumatic,  then  the  position  is  clear,  but  to  judge  by  the 
size  of  granulations,  by  the  rupture  of  chordae  tendineae,  by 


UPON  RHEUMATIC  FEVER  183 

the  spread  of  the  vegetations  on  to  the  surface  of  the  auricle, 
or  by  the  marked  affection  of  the  tricuspid  valve,  is,  we  believe, 
dangerous  and  liable  to  result  in  an  attempt  to  limit  a  disease 
which  is  perhaps  of  all  diseases  one  of  the  most  variable. 
This  fact  we  can  state,  that  we  have  succeeded  in  isolating 
a  diplococcus  from  cases  of  malignant  endocarditis  in  which 
rheumatism  appeared  to  be  the  only  cause,  and  have  repro- 
duced in  animals,  even  to  the  very  identical  valves,  a  malignant 
endocarditis,  and  then  later  a  condition  indistinguishable,  as 
far  as  the  arthritis  and  endocarditis  are  concerned,  from  that 
produced  by  the  diplococcus  of  simple  rheumatism.  Clinical 
observation  has  also  demonstrated  that  no  line  can  be  drawn 
between  simple  rheumatic  endocarditis  and  the  malignant 
types  as  observed  in  man. 

The  occurrence  of  ante-mortem  thrombosis  in  the  heart  in 
rheumatic  fever.  The  causes  of  its  occurrences  are  probably 
various — there  are  the  mechanical  difficulties  associated  with 
the  endocarditis,  there  is  the  weakness  of  the  heart  wall,  and 
the  increased  tendency  of  the  blood  to  clot.  In  rabbits  the 
stages  of  the  process  can  be  studied.  In  one  case  we  noted 
rapid,  feeble,  distant  heart  sounds  and  the  development  of  a 
systolic  murmur,  audible  at  the  lower  angle  of  the  right 
scapula.  We  were  puzzled  by  the  murmur,  and  suspected, 
from  the  condition  of  the  heart,  pericarditis.  The  necropsy 
showed  no  gross  valvular  disease,  but  a  large  ante-mortem 
clot  in  the  right  auricle.  It  is  clear  that  in  this  case  one  factor 
in  the  causation  of  ante-mortem  thrombosis  could  be  excluded 
—namely  the  mechanical  one  due  to  advanced  valvular  disease. 
The  next  case  in  which  we  noted  the  feeble,  distant  heart  sounds 
we  did  not  wait,  but  after  assuring  ourselves  that  it  was  not 
a  passing  phenomenon  the  animal  was  killed  and  the  heart 
examined.  Ante-mortem  thrombosis  had  commenced  in  the 
left  ventricle  in  the  neighbourhood  of  the  valve  ring  beneath 
the  mitral  cusps  and  at  the  apex  of  the  left  ventricle.  There 
was  no  gross  valvular  lesion.  Finally,  just  as  in  man  a  mitral 
systolic  murmur  may  appear  early  in  the  illness  and  then 
rapidly  disappear,  so  in  rabbits  we  have  observed  the  same 
phenomenon  and  have  ascribed  it  to  the  same  cause- — namely, 
to  an  acute  dilatation  of  the  ventricle  rather  than  to  an  organic 
affection  of  the  mitral  valve. 


184  FURTHER  INVESTIGATIONS 


REFERENCES 

1  "  New  Sydenham  Society's  Year-book,"   1863,  Summary  by  Dr. 
Handfield- Jones. 

2  London  Hospital  Reports,   1864,  vol.  i,  p.  459;  Lancet,  November 
26,  1864,  p.  606. 

3  "  Note  on  the    '  Embolic  '  Theory  of  Chorea,"  Brit.  Med.  Jour., 
December  23,  1876. 

4  Brit.  Med.  Jour.,  vol.  i,  1865. 

5  British  and  Foreign  Medical  and  Chirurgical  Review,  p.  506  ;    St. 
Bartholomew's  Hospital  Reports,  vol.  v. 

6  Transactions  of  the  Royal  Medical  and  Chirurgical  Society,  1876. 

7  Bastian,    "Remarks   on   the    Pathology   of   Chorea,"    Brit.    Med. 
Jour.,  January  13  and  20,  1877. 

8  Chorea,  "  System  of  Medicine,"  Albutt,  vol.  vii. 

9  Raymond,  Bulletin  Medical,  Paris,  1896,  vol.  x. 

10  "  Pathological  Anatomy  of  Chorea,"  Brain,  1890. 

11  Ibid. 

12  Transactions  of  the  Pathological  Society  of  London,  1892,  vol.  xliii. 

13  American  Journal  of  Medical  Science,  1894,  p.  31. 

14  "  Manifestations  of  the   Rheumatic   State,"   Harveian  Lectures. 
1888. 

13  Atti    dell'    XI.    Congresso    Medico    Internazionale,    Rome,    1894, 
vol.  iii. 

16  "  Manual  of  Diseases  of  the  Nervous  System,"  1893,  P-  854. 

17  "  Cortical  Changes  in  Acute  Chorea,"  Transactions  of  the  Pathological 
Society,   1900. 

18  Chorea,  "System  of  Medicine  "  (Allbutt),  vol.  vii. 

19  La  Natura  infettura  delta  Corea  del  Sydenham,  Napoli,  1893. 

20  "  The  Microbic  Origin  of  Chorea,"  American  Journal  of  the  Medical 
Sciences,  1894,  p.  31. 

21  Comptes  Rendus   de  la   Societe  de   Biologie,   Paris,   J898,    vol.    v, 
p.    128. 

22  Ibid.  1898,  vol.  v,  p.  214. 

23  Berliner  Klinische  Wochenschrift,  1899,  No.  29,  p.  638. 

24  Centralblatt  fur  Innere  Medicin,  1899,  Band  XX,  p.  489. 

25  Transactions  of  the  Pathological  Society,  October  1900. 

26  The  Lancet,  September  29,  1888,  p.  605. 

27  "  A  Treatise  on  Rheumatism." 

28  "  Tonsillitis  in  Rheumatic  States." 

29  A  Paper  read  before  the  Society  for  Innere  Medicin,  Berlin,  1901. 


PAPER  NO.  XV 

A   CONTRIBUTION   TO   THE   STUDY   OF 
MALIGNANT  ENDOCARDITIS 

(From  vol.  85  of  the  Medico-Chirurgical  Transactions.) 

This  paper  was  the  result  of  some  years  of  investigation,  and  is 
concerned  with  the  difficult  problem  of  the  relation  of  malignant  endo- 
carditis to  simple  rheumatic  endocarditis — clearly  a  question  of  the 
greatest  practical  importance  in  general  medicine,  and  one  realised  by 
all  who  are  alive  to  the  great  frequency  of  rheumatic  heart  disease. 
The  relation  of  the  two  processes  was  brought  at  once  into  prominence 
when  the  infective  nature  of  acute  rheumatism  was  determined,  for  it 
compelled  us  to  picture  the  possible  results  of  such  an  infection  when 
it  was  located  in  a  valve.  The  two  essential  questions  to  be  answered 
are  :  Is  it  probable  or  even  possible  that  the  rheumatic  infection, 
belonging  as  it  does  to  the  group  of  streptococci,  will  produce  valvular 
lesions  that  will  always  run  a  benign  course  ?  Secondly,  if  they 
do  not,  what  result  will  follow  ?  The  solution  offered  here,  which 
may  be  studied  more  fully  by  the  light  of  our  later  paper,  No.  XXIII, 
is  that  acute  rheumatic  endocarditis  may  show  all  grades  of  virulence 
and  may  in  itself,  without  any  added  infection,  be  a  cause  of  malignant 
endocarditis.  This  statement  does  not  imply  that  all  malignant 
endocarditis  is  rheumatic  in  origin  or  that  on  occasions  some  other 
infection  may  not  cause  a  malignant  endocarditis  in  a  patient  who 
has  previously  suffered  from  a  rheumatic  endocarditis. 

In  1903  Dr.  Ainley  Walker  and  Dr.  Beaton  published  an  important 
contribution  to  the  bacteriology  of  acute  rheumatism  which  supported 
our  investigations. 

I.  Introductory  Outline 

(a)  A  Group  of  Cases  of  Malignant  Endocarditis  closely  associated 
with  Rheumatic  Fever 

While  investigating  the  pathogenesis  of  rheumatic  fever, 
our  attention  has  been  directed  to  certain  cases  of  progressive 
heart  disease  which  run  a  more  or  less  prolonged  course,  and 

iS; 


186        STUDY  OF  MALIGNANT  ENDOCARDITIS 

terminate  almost  invariably  in  death.  After  death  it  is  found 
that  the  valves  of  the  heart  are  very  extensively  diseased, 
and  that  the  morbid  process  is  often  extremely  active.  Among 
such  cases  there  is  one  group  in  which  we  were  particularly 
interested,  for  previous  to  the  fatal  illness  there  had  been  a 
history  of  rheumatic  fever  ;  sometimes  there  had  been  repeated 
attacks,  and  during  the  last  illness  symptoms  had  arisen  which 
suggested  that  rheumatism  of  some  unusual  type  was  in 
reality  the  true  excitant.  The  symptoms  in  these  cases 
arose  insidiously,  and  there  was  no  local  focus  of  suppura- 
tion, no  wound  or  other  demonstrable  cause  which  may  be 
considered  to  have  been  the  starting-point  of  this  progressive 
form  of  heart  disease.  This  class  of  case  is  well  recognised, 
for  it  is  a  comparatively  common  one  in  the  large  hospitals. 
It  is  possible  in  some  instances  to  detect  the  nature  of  the 
disease  even  early  in  the  illness,  because  of  the  persistently 
excited  action  of  the  heart  and  loudness  of  a  systolic  murmur  ; 
but,  on  the  other  hand,  even  when  death  has  occurred,  several 
observers  of  equal  acumen,  and  with  the  same  advantages 
in  the  study  of  the  case,  may  differ  in  their  opinion  as  to  whether 
the  condition  is  one  of  rheumatic  morbus  cordis  or  so-called 
"  infective  endocarditis."  No  doubt  the  great  majority  of 
these  cases  as  they  progress  diverge  more  and  more  from 
the  appearance  of  rheumatic  fever,  and  the  force  of  the 
disease  falls  so  exclusively  upon  the  cardiac  valves  that  it 
may  be  difficult  in  the  end  to  detect  any  clinical  resemblance  ; 
but  it  is  equally  certain  that  the  more  these  cases  are  care- 
fully studied,  the  more  difficult  it  is  to  say  where  a  distinctive 
line  can  be  drawn  between  them  and  acute  rheumatism. 
Anaemia,  prostration,  wasting,  pyrexia,  and  infarction  are 
very  frequent  and  important  symptoms  in  this  disease,  but 
there  is  not  one  of  these  which  may  not  occur,  to  a  lesser 
degree,  in  severe  rheumatic  fever.  In  these  cases,  again, 
suppuration  does  not  occur  even  in  the  blood-clot  of  the 
aneurysms  that  may  result,  but  numerous  white  infarcts 
are  often  found  in  the  kidneys,  lungs,  or  spleen  after  death. 

(b)  "  Malignant  "  Preferable  to  "  Infective  "  as  a  Title  for  this 
Form  of  Endocarditis 

The  usual  procedure  in  this  country  is  to  describe  such 
cases   as   examples   of    "  infective    endocarditis,"    and   if   by 


STUDY  OF  MALIGNANT  ENDOCARDITIS        187 

this  term  no  suggestion  were  implied  that  rheumatic  endo- 
carditis was  non-infective,  the  description  would  be  an  excellent 
one.  It  is  unfortunate  that  such  is  not  the  case,  but  that 
through  no  fault  in  the  term  itself  the  name  in  question  has 
been  widely  used  in  contradistinction  to  rheumatic  endo- 
carditis ;  and  this  is  the  more  strange  because  for  several 
years  rheumatic  fever  has,  in  spite  of  the  absence  of  actual 
proof,  been  looked  upon  as  due  to  an  infection. 

For  this  condition  the  name  malignant  endocarditis  seems 
to  us  preferable,  for  whether  it  proves  fatal  or  not,  the  type 
is  malignant. 

(c)  Researches  of  other  Investigators  upon  Malignant 

Endocarditis 

An  immense  amount  of  research  has  been  devoted  to  the 
study  of  malignant  endocarditis,  and  it  would  be  impossible 
in  such  a  paper  as  this  to  mention  the  names  of  the  many 
investigators.  Their  results  have  been  of  far-reaching  im- 
portance. They  have  definitely  settled  the  microbic  origin 
of  the  condition.  They  have  also  shown  that  various  micro- 
organisms may  give  rise  to  malignant  endocarditis,  but  that 
the  most  usual  cause  is  a  streptococcus.  Experiments  upon 
animals  have  resulted  in  the  reproduction  of  the  disease, 
though  not  with  constancy,  and  in  some  cases  the  cardiac 
valves  have  been  damaged  mechanically  before  endocarditis 
has  resulted.  It  may  be  justly  asserted  that  these  investi- 
gators have  elucidated  the  broad  outlines  of  the  pathology 
of  malignant  endocarditis,  though  there  are  several  difficult 
problems  yet  to  be  solved,  among  which  is  the  relation  of 
such  cases  to  rheumatic  fever. 

(d)  Renewed  Investigation  of  Malignant  Endocarditis 

Desirable 

Heretofore  it  has  not  been  possible  to  solve  this  problem, 
for  there  has  been  no  agreement  upon  the  cause  of  rheumatic 
fever.  The  outcome  of  this  limitation  of  knowledge  has  been 
the  widespread  belief  that  malignant  endocarditis  in  a  rheu- 
matic patient  is  invariably  a  result  of  some  secondary  infection 
of  the  tissues  injured  by  previous  rheumatism.  Nevertheless 
there  have  been  some  clinicians  and  pathologists  who  have 


188        STUDY  OF  MALIGNANT  ENDOCARDITIS 

felt  this  attitude  to  be  too  rigid,  and  have,  without  the  means 
of  bringing  forward  complete  proof,  believed  that  some  cases 
are  truly  rheumatic  in  origin.  At  the  present  time  so  much 
evidence  has  been  obtained  in  favour  of  rheumatic  fever 
being  the  result  of  a  diplococcus  infection,  that  it  seems  a 
proper  occasion  to  investigate  once  more  this  question  of  the 
relation  of  the  two  diseases. 

(e)  The  Result  of  the  Authors'  Investigations 

It  is  this  investigation  with  which  our  paper  is  concerned, 
and  our  conclusion  can  be  shortly  stated  thus  :  That  there  is  a 
group  of  cases  of  malignant  endocarditis  which  is  rheumatic  in 
nature.  How  comprehensive  this  group  will  prove  to  be 
further  investigations  alone  can  decide. 

Before  we  summarise  the  reasons  for  this  conclusion  we 
are  anxious  to  make  clear  the  scope  of  our  paper.  We  do 
not  claim  that  the  view  that  rheumatic  fever  is  a  cause  of 
malignant  endocarditis  is  an  original  one  ;  we  are  well  aware 
that  others — as,  for  example,  Ogle,  Osier,  Peter,  Burkart, 
and  Fernet — have  entertained  this  opinion  ;  that  others 
before  us  have  demonstrated  that  organisms  similar  in  their 
morphology  may  occur  in  the  two  diseases,  and  have  felt 
that  in  some  instances  no  clinical  distinctions  can  be  drawn 
between  simple  and  malignant  endocarditis.  Our  paper,  as  its 
title  claims,  is  but  a  contribution  to  the  study  of  malignant 
endocarditis,  and  affords,  we  believe,  a  strong  support  of 
the  view  that  malignant  endocarditis  may  be  of  rheumatic 
origin. 

(f)  Reasons  for  the  A  ssertion  that  there  is  a  Malignant  Rheumatic 

Endocarditis 

The  chief  reasons  upon  which  we  rely  for  support  of  our 
assertion  can  be  summarised  thus  : 

Firstly.  The  probability  that  some  of  these  cases  are 
rheumatic  is  in  accord  with  clinical  experience. 

The  clinical  cases  we  record  will  bear  out  this  statement. 

Secondly.  The  probability  that  some  of  these  are  rheumatic 
is  in  accord  with  pathological  experience. 

The  minute  investigation  of  the  morbid  anatomy  of  the 
clinical  cases  we  record  supports  this  conclusion. 

Thirdly.     The    probability   that    some    of   these   cases   are 


STUDY  OF  MALIGNANT  ENDOCARDITIS        189 

rheumatic  is  in  our  opinion  in  accord  with  bacteriological 
experience,  for — 

1.  A  diplococcus  is  a  cause  of  rheumatic  fever. 

2.  A  diplococcus  can  be  isolated  in  pure  culture  from  these 
cases  of  malignant  endocarditis,  which  will  reproduce  the 
disease  in  rabbits. 

3.  The  culture  and  morphological  characteristics  of  these 
two  diplococci  resemble  one  another  so  closely  as  to  lead 
to  the  conclusion  that  they  are  identical  organisms. 

4.  The  Diplococcus  rheumaticus  will  produce  malignant  endo- 
carditis, indistinguishable  from  that  produced  by  the  diplococcus 
isolated  from  certain  cases  of  malignant  endocarditis  in 
man. 

5.  The  Di-plococcus  rheumaticus  may  produce  in  a  rabbit 
first  a  recoverable  illness  with  the  manifestations  of  rheu- 
matic fever,  and  then  on  a  second  inoculation  malignant 
endocarditis. 

6.  A  diplococcus  isolated  from  certain  cases  of  malignant 
endocarditis  in  man  will  produce  not  only  malignant  endo- 
carditis in  rabbits,  but  a  condition  indistinguishable  from  the 
disease  we  believe  to  be  rheumatic  fever. 

7.  By  these  diplococci,  every  grade  of  endocarditis  from 
simple  to  malignant,  and  from  malignant  to  simple,  can  be 
produced,  as  our  macroscopic  specimens  bear  witness. 

II.  The  Investigation 

(a)  Clinical,  Experimental,  and  Pathological  Observations 

The  first  case  will  make  clear  the  type  we  are  studying. 

Case  i.  A  child,  aged  n,  was  admitted  to  St.  Mary's 
Hospital,  under  the  care  of  Dr.  W.  B.  Cheadle,  upon 
October  22,  1897,  and  died  November  12.  When  three  and 
a  half  years  of  age  he  had  suffered  from  rheumatic  fever, 
and  when  five  and  a  half  from  scarlet  fever.  His  mother 
had  suffered  from  rheumatic  fever.  Five  weeks  before  admis- 
sion there  had  been  swelling  of  the  knees  and  ankles,  and  for 
five  months  there  had  been  complaints  of  obscure  pains  in 
the  chest  and  abdomen.  There  was  no  history  of  an  injury, 
no  suppurating  focus,  and  no  obvious  cause  which  could  be 
looked  upon  as  an  explanation  of  some  secondary  infection. 
Upon  admission  the  boy  was  very  anaemic,  the  temperature 


igo        STUDY  OF  MALIGNANT  ENDOCARDITIS 

was  100.80  F.,  pulse  ioo,  respirations  28.  The  heart  was  much 
enlarged,  there  was  a  loud  systolic  mitral  murmur,  and  also 
an  aortic  systolic  murmur.  The  liver  and  spleen  were  enlarged, 
the  urine  was  natural.  Soon  after  admission  crepitations 
were  heard  at  the  base  of  the  left  lung  posteriorly,  and  there 
was  pain  in  the  left  side. 

Upon  October  28  blood  and  albumen  were  found  in  the  urine, 
and  until  death  upon  November  12  there  was  irregular  pyrexia. 
Hematuria  became  persistent,  and  casts  were  found  in  the 
urine.  There  was  pain  over  the  spleen,  and  progressive  en- 
largement of  that  organ.  Purpura,  vomiting,  progressive 
anaemia,  emaciation,  and  sweating  were  prominent  symptoms, 
and  finally  the  pulse  became  irregular  and  intermittent,  and 
death  resulted  from  cardiac  failure. 

The  necropsy  showed  recent  pericarditis,  with  two  ounces 
of  fluid  in  the  pericardium,  which  contained  a  few  flakes. 
There  was  extensive  ulceration  of  both  flaps  of  the  mitral 
valve,  and  exuberant  granulations  spread  over  the  surface  of 
the  auricle.  The  valves  upon  the  right  side  of  the  heart  were 
not  affected  ;  the  heart  itself  was  hypertrophied  and  dilated. 
There  were  numerous  white  infarcts  in  the  spleen,  with  peri- 
splenitis ;  it  was  soft,  and  weighed  five  ounces.  There  were 
numerous  white  infarcts  in  the  kidneys,  but  none  found  in 
the  lungs.  Numerous  subserous  haemorrhages  were  visible 
along  the  intestines.  There  were  no  abscesses,  but  many 
white  infarcts,  as  already  stated.  Numerous  micrococci  were 
found  in  the  granulations. 

We  admit  that  secondary  infections  can  occur  during 
life  without  any  demonstrable  cause,  but  it  seems  to  us  legiti- 
mate to  argue  upon  such  a  case  as  this  in  the  following  way  : 
Rheumatic  fever  is  a  bacterial  disease,  and  one  which  apparently 
does  not  confer  immunity.  Evidence  at  present  points  to 
it  as  the  result  of  a  diplococcic  infection,  and  it  would  appear 
that  the  diplococcus  may  exist  for  long  periods  in  the  body. 

In  such  a  case  as  the  above  there  was  a  family  and  personal 
history  of  rheumatism,  and  such  a  child,  as  all  clinical  expe- 
rience has  shown,  may  be  justly  termed  rheumatic.  If,  then, 
from  such  a  case  a  diplococcus  be  isolated,  it  is  as  legitimate 
to  assume  that  it  may  be  the  Diplococcus  rheumaticus,  under 
some  unusual  conditions,  as  to  assume  a  secondary  infection. 
The  proof  must  rest  upon  an  accurate  study  of  the  micro- 


STUDY  OF  MALIGNANT  ENDOCARDITIS        191 

organism  which  is  isolated,   by   various   methods,  including 
among  these  the  method  of  experiment. 

Case  2.  The  next  case  was  that  of  a  woman  aged  50, 
who  was  admitted  to  St.  Mary's  Hospital,  under  Dr.  W.  B. 
Cheadle,  in  June  1898,  for  dyspnoea  of  some  months'  duration. 
The  only  cause  that  was  given  for  this  dyspnoea  was  an  attack 
of  rheumatic  fever  eight  years  previously.  Upon  admission 
she  was  cyanosed  and  short  of  breath,  and  complained  of  pain 
in  the  left  side.  There  was  orthopncea.  The  temperature 
was  102.80  F.,  pulse  103,  respiration  40.  The  heart  was  much 
enlarged,  and  there  was  a  mitral  systolic  murmur.  The  hands 
were  deformed  by  previous  attacks  of  rheumatism.  The 
nature  of  the  case  remained  quite  in  doubt,  though  towards  the 
end  irregular  pyrexia,  infarctions  in  the  lungs  and  spleen,  and 
purpura  suggested  the  diagnosis  of  malignant  endocarditis. 

The  necropsy  showed  recent  pericarditis,  adhesive  in  type, 
and  also  old  adhesions,  the  result  of  a  previous  attack. 

The  mitral,  tricuspid,  and  aortic  valves  showed  extensive 
vegetative  endocarditis,  and  there  were  vegetations  over  the 
surface  of  the  left  auricle.  There  were  white  infarcts  in  the 
lungs  and  spleen,  but  none  in  the  kidneys.  There  was  no 
suppuration.  Numerous  micrococci  were  visible  in  the 
granulations. 

The  necropsy  disclosed  characteristic  malignant  endo- 
carditis, yet  clinically  this  case  was  most  obscure,  and  resembled 
at  first  a  severe  rheumatic  morbus  cordis.  It  was  not  until 
the  end  of  the  illness  that  the  malignant  character  of  the 
disease  became  apparent. 

Case  3.  A  patient  aged  16  was  admitted  into  St.  Mary's 
Hospital  in  January  1900  under  Dr.  Lees,  suffering  from 
morbus  cordis.  When  six  years  of  age  he  had  an  attack 
of  rheumatic  fever,  and  since  that  time  had  suffered  from  three 
more  definite  attacks.  His  mother  had  suffered  from  rheu- 
matic fever.  The  final  illness  had  commenced  insidiously, 
with,  pain  round  the  heart,  and  three  weeks  before  admission 
there  had  been  pains  in  the  ankles  and  knees.  No  cause 
was  assigned  for  this  illness,  and  on  special  inquiry  of  the  mother 
she  volunteered  that  she  had  thought  this  was  another  attack  of 
rheumatism,  because  it  commenced  just  as  the  previous 
attacks  had  done. 

On  admission  the  patient  was  very  anaemic  and  wasted, 


IQ2        STUDY  OF  MALIGNANT  ENDOCARDITIS 

and  there  was  irregular  pyrexia,  with  well-marked  mitral 
and  probably  aortic  disease. 

The  course  of  the  illness  was  progressive  and  malignant 
in  type.  Irregular  fever,  enlargement  of  the  spleen,  and 
haematuria,  with  progressive  anaemia  and  emaciation,  were 
the  prominent  symptoms,  and  throughout  the  time  that  the 
patient  was  in  the  hospital  no  doubt  was  entertained  as  to  the 
nature  of  the  illness. 

The  necropsy  showed  a  few  ounces  of  clear  fluid  in  the 
pericardium  ;  the  mitral  valve  was  fringed  with  numerous 
vegetations,  varying  in  size  from  a  pin's  head  to  a  pea.  There 
were  recent  vegetations  upon  the  aortic  valve,  but  the  right 
side  of  the  heart  was  unaffected.  In  the  spleen  there  were 
three  white  infarcts,  and  in  the  left  kidney  one. 

There  was  no  suppuration. 

This  case  was,  in  one  respect,  the  converse  of  the  pre- 
ceding. The  clinical  diagnosis  was  quite  definite,  but  the 
necropsy  showed  a  condition  which,  without  the  clinical 
history  for  a  guide,  could  have  been  explained  as  active 
rheumatic  morbus  cordis,  and  not  as  malignant  endo- 
carditis. 

We  investigated  the  bacteriology  of  this  case,  and  at  first 
intended  to  include  it  (the  resemblance  was  so  striking)  among 
our  first  series  of  cases  of  rheumatic  fever  published  in  the 
Lancet  in  September  1900  ;  but  we  finally  concluded,  before 
publication,  that  it  was  better  to  exclude  a  border-line  case 
of  this  kind,  and  have  not  made  allusion  to  it  until  the  present 
paper. 

The  bacteriological  investigations  resulted  as  follows  : 

Numerous  diplococci  growing  in  chains  were  demonstrated 
in  films  made  from  the  granulations  on  the  mitral  valve,  and 
cultures  were  made  with  the  following  media  :  agar,  ascitic 
fluid,  acid  and  alkaline  bouillon  slightly  acidified  with  lactic 
acid.  The  liquid  media  were  incubated  both  aerobically  and 
anaerobically. 

Twenty-four  hours  afterwards  the  results  were  as  follows  : 

Upon  agar,  a  poor  growth  of  minute  discrete  colonies 
consisting  of  extremely  minute  diplococci.  The  pork  medium 
and  ascitic  fluid  were  sterile.  The  alkaline  bouillon  showed  a 
very  poor  growth  of  minute  diplococci. 

The  acid  milk,  both  aerobically  and  anaerobically,  showed 


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STUDY  OF  MALIGNANT  ENDOCARDITIS        193 

a  vigorous  growth  of  diplococci  in  chains.  This  diplococcus 
was  grown  in  the  milk  medium  by  means  of  sub-cultures  for 
two  months.  From  the  original  tubes  a  sub-culture  was 
made  upon  blood-agar,  and  upon  two  occasions  the  contents 
of  one  blood-agar  tube  was  injected  into  the  auricular  vein 
of  a  rabbit.     The  result  in  each  case  was  negative. 

The  isolation  of  a  minute  diplococcus  from  a  case  such  as 
this  is  in  accord  with  the  experience  of  Professor  Litten,1 
who  also  isolated  a  minute  diplococcus  from  a  condition 
which  he  termed  the  malignant  non-septic  form  of  rheumatic 
endocarditis.  Such  cases  as  these  he  considered  to  be  charac- 
terised by  pyrexia,  infarction,  pallor,  and  sweating,  with 
haematuria  and  enlargement  of  the  spleen,  but  no  suppuration. 

Professor  Litten  was  inclined  to  the  view  that  this  diplo- 
coccus was  probably  not  identical  with  the  diplococcus  de- 
scribed by  Professor  Wassermann  2  as  the  cause  of  rheumatic 
fever.  We  believe  that  the  diplococcus  we  isolated  in  this 
case  is  identical  with  the  diplococcus  which  we  have  now  isolated 
from  twenty  cases  of  rheumatic  fever. 

Case  4.  This  fourth  case,  although  a  case  of  rheumatic 
fever,  we  mention  here  because  it  resembled  malignant  endo- 
carditis in  this  respect,  that  during  life  upon  two  occasions 
diplococci  growing  in  chains  were  isolated  from  the  blood. 
The  patient  was  under  the  care  of  Dr.  D.  B.  Lees,  and  the  case 
is  described  in  Paper  No.  VII.  We  naturally  thought  at  that 
time  that  the  case  was  one  of  malignant  septic  endocarditis, 
because  we  isolated  streptococci  from  the  blood  during  life, 
though  previous  investigations  had  made  us  somewhat  doubtful 
of  the  validity  of  this  conclusion.  The  clinical  history,  the 
course  and  character  of  the  disease,  and  the  result  of  the 
necropsy  proved  conclusively  that  it  was  a  case  of  severe 
rheumatic  fever.  Though  a  most  severe  case  of  rheumatic 
fever  with  numerous  and  severe  local  lesions  there  was  no 
suppuration,  and  yet  during  life  there  was  a  streptococcus, 
or,  to  be  more  exact,  a  diplococcus  which  grew  in  chains, 
circulating  in  the  blood  stream. 

Case  5.  A  boy  aged  10  was  admitted  to  St.  Mary's  Hospital 
in  April  1900,  for  heart  disease,  under  the  care  of  Dr.  W.  B. 
Cheadle.  Six  weeks  before  admission  he  had  suffered  from 
pain  over  the  heart,  sweating,  and  attacks  of  diarrhoea.  A 
year  previous  to  this  he  had  been  in  the  hospital  for  an  attack 

13 


194        STUDY  OF  MALIGNANT  ENDOCARDITIS 

of  rheumatic  fever,  and  one  brother  had  also  suffered  from 
rheumatic  fever.  On  admission  aortic  and  mitral  endo- 
carditis were  discovered,  and  a  very  noticeable  feature  was 
extensive  muscular  wasting. 

Upon  April  30  he  developed  pericarditis. 

In  May  there  was  arthritis,  the  ankles  and  knees  being 
affected.  There  were  also  diarrhoea  and  vomiting.  In 
June  crepitations  were  detected  in  the  lungs.  In  July 
infarction,  sweating,  and  wasting  were  prominent,  and  death 
occurred  in  July,  after  eighty-eight  days  of  irregular  pyrexia. 

This  appeared  to  us  during  life  to  be  a  classical  case  of 
rheumatic  malignant  endocarditis. 

There  was  unfortunately  no  opportunity  of  obtaining  a 
complete  necropsy,  but  the  heart  was  removed,  and  the 
pericardium  was  found  generally  adherent.  The  heart  itself 
was  very  little  enlarged,  but  upon  the  mitral  and  aortic  valves 
and  on  the  wall  of  the  left  auricle  there  were  extensive  and 
exuberant  granulations.  The  right  side  was  not  affected. 
Films  from  the  vegetations  showed  minute  diplococci  in  chains. 
Aerobic  cultures  in  the  milk  medium  were  obtained  and 
transferred  to  blood  agar.  A  series  of  important  experimental 
results  followed. 

The  growth  from  six  tubes  was  intravenously  injected 
into  a  rabbit  on  July  28,  and  upon  July  31  and  August  1 
the  left  knee-joint  and  left  shoulder-joint  were  swollen.  The 
animal  died  suddenly  upon  the  fifth  day.  The  necropsy 
showed  exuberant  granulations  upon  identical  valves,  namely 
the  aortic  and  mitral.  The  micro-organisms  were  demonstrated 
in  great  numbers  in  the  damaged  valves. 

In  thus  reproducing  malignant  endocarditis  without  any 
previous  injury  to  the  cardiac  valves,  we  confirmed  the  classical 
investigations  of  Dreschfeld,  Ribbert,  Bonome,  Roux,  Manna- 
berg,  and  others.  It  will  also  be  apparent  that  in  the  course 
of  this  investigation  we  have  confirmed  the  results  of  other 
observers  by  the  experimental  production  of  infarction  and 
haemorrhages. 

Upon  August  8  a  second  inoculation,  from  a  culture  obtained 

from  this  rabbit,  was  made  into  a  smaller  animal.     Death 

occurred  upon  the  fifth  day  from  vegetative  aortic  endocarditis. 

No  other  valve  was  affected. 

The  cultures  from  this  rabbit  were  contaminated  with  the 


STUDY  OF  MALIGNANT  ENDOCARDITIS        195 

Bacillus  coli,  so  recourse  was  had  to  the  original  culture,  and 
a  third  inoculation  made  with  a  smaller  quantity  of  the 
organism. 

Death  occurred  on  the  nineteenth  day.  There  was  arthritis 
of  the  right  knee  and  diarrhoea,  but  no  clinical  evidence 
of  endocarditis  or  pericarditis.  Death  occurred  from  gradual 
cardiac  failure  due  to  dilatation  and  fatty  degeneration  of 
the  heart  muscle  with  ante-mortem  thrombosis.  In  this 
case  it  will  be  observed  there  was  no  manifestation  of  malignant 
endocarditis,  but  the  necropsy  showed  a  simple  endocarditis. 

A  larger  quantity  of  the  original  culture  was  used  for  a 
fourth  injection. 

Death  occurred  on  the  tenth  day.  During  life  there  were 
noted  diarrhoea,  heart  disease,  and  arthritis  of  the  right 
shoulder-joint.  The  necropsy  showed  well-marked  malignant 
mitral  endocarditis,  white  infarcts  in  both  kidneys  and  in  the 
spleen,  but  no  pericarditis. 

A  smaller  quantity  of  the  original  culture  was  injected 
into  a  fifth  rabbit,  which  was  killed — for  it  was  moribund — 
upon  the  tenth  day.  During  life  diarrhoea,  pericarditis,  and 
arthritis  were  noted. 

The  necropsy  confirmed  that  this  condition  was  one  of 
rheumatic  fever. 

The  culture  from  this  case  was  injected  into  a  sixth 
rabbit,  and  death  occurred  upon  the  tenth  day.  There  was 
arthritis,  but  no  valvulitis.  The  heart's  action  was,  however, 
extremely  rapid,  and  for  some  days  there  was  a  mitral  systolic 
murmur. 

It  is  evident  from  this  series  of  inoculations  that  in  three 
instances  definite  malignant  endocarditis  resulted,  in  two 
death  occurred  from  cardiac  failure — without  malignant 
endocarditis — and  in  one  case  death  occurred  from  peri- 
carditis. 

Arthritis  was  frequent.  One  symptom  occurred  which 
we  had  not  noticed  in  rabbits  inoculated  with  the  Diftlo- 
coccus  rheumaticus  from  rheumatic  fever,  namely  diarrhoea  ; 
and  this  we  know  occurs  not  infrequently  in  man  during 
the  course  of  malignant  endocarditis,  and  was  a  prominent 
symptom  in  the  case  from  which  this  organism  was  isolated. 

Case  6.  A  boy  aged  13  was  admitted  into  St.  Mary's 
Hospital,    November    1900,    for     morbus    cordis,    under   the 


196        STUDY  OF  MALIGNANT  ENDOCARDITIS 

care  of  Dr.  Lees.  Six  years  before  he  had  suffered  from 
enteric  fever,  and  three  years  before  from  pneumonia  and 
rheumatic  fever.  He  had  been  ailing  for  two  months  previous 
to  admission,  and  had  suffered  from  pains  in  the  chest  and 
abdomen.  The  boy  was  pale  and  sallow,  but  well  nourished  ; 
there  was  mitral  and  aortic  disease,  and  an  enlarged  spleen. 
He  remained  in  the  hospital  until  his  death  in  January,  and 
during  that  time  there  was  usually  irregular  pyrexia,  though 
sometimes  for  days  the  temperature  remained  normal.  Death 
was  sudden. 

The  necropsy  showed  general  pericardial  adhesion,  and 
fungating  masses  of  vegetation  upon  the  mitral  and  aortic 
valves.  There  were  petechiae  under  the  capsule  of  the  liver. 
The  spleen  weighed  fifteen  ounces,  was  tough  in  consistence, 
and  contained  one  recent  infarct.  There  were  numerous 
small  haemorrhages  in  the  cortices  of  both  kidneys.  There 
was  no  suppuration.  Two  hours  after  death  the  mitral 
valve  was  exposed,  and  four  tubes  of  the  acid  milk  medium 
inoculated  with  fragments  of  the  granulations.  In  two  out 
of  four  there  was  a  pure  growth  of  very  small  diplococci 
growing  in  chains.     Two  were  sterile. 

Upon  January  24  the  growth  from  six  small  tubes  was 
injected  into  a  rabbit  at  1  noon. 

At  3  o'clock  the  temperature  had  risen  to  105. 2°,  and  a 
blowing  systolic  murmur  was  audible. 

During  the  rest  of  January  the  temperature  was  raised, 
there  was  some  diarrhoea,  and  the  heart  was  rapid. 

During  February  there  was  improvement,  but  occasional 
fever. 

During  March  improvement  continued. 
Upon  April  8  the  hind  limbs  were  found  completely  paralysed, 
and  there  was  complete  incontinence  and  loss  of  tone  of  the 
anal  sphincter.  The  diplococci  were  isolated  from  the  urine 
and  the  animal  was  killed.  There  was  no  definite  endocarditis 
or  pericarditis,  and  nothing  to  be  found  in  the  other  viscera 
of  importance  except  a  haemorrhage  into  the  pia  mater  some 
quarter  of  an  inch  in  vertical  extent  immediately  above  the 
lumbar  enlargement. 

It  will  be  noticed  that  whether  because  the  resistance  of 
the  animal  was  unusually  great,  or  the  initial  inoculation 
not  sufficient,  the  disease  was  not  reproduced  ;   but  the  length 


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STUDY  OF  MALIGNANT  ENDOCARDITIS       197 

of  time  (ten  weeks)  that  the  diplococci  remained  active  in 
the  body  is  a  point  of  much  interest. 

Another  inoculation  from  the  original  culture  was  made 
upon  January  25,  a  day  after  the  former  inoculation,  into 
a  rabbit  of  smaller  size.  The  animal  was  killed  upon  the 
tenth  day ;  during  life  there  were  pyrexia  and  morbus 
cordis. 

The  necropsy  showed  well-marked  vegetative  mitral  endo- 
carditis, petechias  in  the  heart  wall,  a  white  infarct  which 
was  softening  in  the  left  kidney,  also  white  infarcts  in  the  right 
kidney  and  spleen. 

A  pure  growth  of  the  diplococcus  was  obtained  from  the 
blood  in  the  heart. 

The  third  rabbit  was  inoculated  from  a  culture  from  the 
preceding,  and  died  in  the  night  of  the  third  day.  The  heart 
throughout  the  illness  was  extremely  excited. 

The  necropsy  showed  the  nearest  approach  to  septicaemia 
we  have  seen  with  this  diplococcus.  Except  for  a  minute 
granulation  upon  the  aortic  flap  of  the  mitral  and  early  peri- 
tonitis, there  was  no  local  lesion  to  be  seen.  Numerous 
diplococci  were  present  in  the  granulation.  There  was  excess 
of  fluid  in  the  pericardium,  and  numerous  diplococci  were 
present  in  the  pericardial-  tissues. 

The  liver  was  pale  ;  the  kidneys  pale  ;  the  spleen  large,  soft, 
and  dark.     The  lungs  showed  no  definite  changes. 

A  fourth  rabbit  was  inoculated  with  a  culture  from  the 
preceding,  and  death  ensued  upon  the  sixth  day.  The  necropsy 
showed  pericarditis,  with  a  fibrino-cellular  exudation  ;  slight 
mitral  endocarditis,  a  small  white  infarct  in  the  left  kidney,  and 
some  perisplenitis- — a  condition  of  rheumatic  fever. 

A  fifth  rabbit  was  inoculated  with  a  culture  from  the  fourth, 
and  died  on  the  fourteenth  day  of  severe  pericarditis.  The 
necropsy  showed  general  recent  pericardial  adhesion,  and  a 
condition  which  resembled  the  severe  general  plastic  peri- 
carditis in  the  rheumatic  fever  of  childhood. 

There  was  no  endocarditis. 

Thus  again  it  will  be  seen  that  both  malignant  endocarditis 
and  a  condition,  we  believe,  indistinguishable  from  rheumatic 
fever  had  been  produced  by  inoculations  of  this  diplococcus. 

This  concludes  our  clinical  investigations,  though  we  would 
emphasise  the  fact  that  in  some  of  these  cases  of  malignant 


198        STUDY  OF  MALIGNANT  ENDOCARDITIS 

endocarditis  in  rheumatic  subjects  rigors  may  occur  for  many 
weeks,  yet  after  death  not  a  trace  of  suppuration  be  found, 
and  infarcts  be  discovered  to  be  cicatrising.  We  have  also 
obtained  from  post-mortem  records  thirty  cases  of  malignant 
endocarditis  without  the  mention  of  an  abscess  in  any  one, 
and  all  of  them  giving  a  previous  history  of  rheumatic  fever. 

The  next  experiment  illustrates  that  a  culture  originally 
obtained  from  a  case  of  rheumatic  fever  may  produce  the 
malignant  type  of  endocarditis  after  it  has  been  passed  through 
thirteen  rabbits. 

In  June  1901  an  intravenous  injection  was  made  into  a 
rabbit  from  a  culture  which  was  the  direct  descendant  of 
the  original  one  obtained  from  the  pericardial  fluid  of  a  fatal 
case  of  rheumatic  fever  in  March  1900. 

A  very  loud  mitral  murmur  developed  upon  the  seventh 
day,  and  the  animal  died  upon  the  eighth.  The  necropsy 
showed  that  there  was  a  large  fungating  vegetation  upon 
the  mitral  valve,  with  white  infarcts  in  the  kidneys  and  spleen 
and  one  small  one  on  the  liver.  The  condition  was  one  of 
characteristic  malignant  endocarditis. 

The  next  experiment  proves  that  a  rabbit  may  survive 
a  first  inoculation  with  the  diplococcus  of  rheumatic  fever, 
recover  completely,  except  for  a  slight  thickening  of  the 
mitral  valve,  and  then  may  die  from  malignant  endocarditis, 
the  result  of  a  second  inoculation. 

The  first  injection  was  made  from  a  culture  of  the  diplo- 
coccus obtained  from  a  boy  suffering  from  acute  rheumatic 
pericarditis.  Treatment  had  necessitated  a  venesection,  and 
the  organism  was  isolated  from  the  blood  of  the  living  patient. 

The  injection  was  made  upon  March  27,  1900,  and  four  days 
afterwards  there  was  arthritis  of  the  right  knee-joint.  Later 
the  animal  became  thinner  and  irritable,  both  knee-joints 
were  affected,  and  the  heart  sounds  were  very  rapid  and  weak. 
In  May  recovery  commenced,  and  eventually  the  animal 
regained  health. 

Six  months  after  recovery  from  the  previous  illness  the 
second  inoculation  was  made,  upon  January  30,  1901.  The 
culture  used  was  from  the  pericardial  exudation  of  a  fatal 
case  of  rheumatic  pericarditis.  The  original  growth  had 
been  obtained  in  the  pericardial  fluid  itself  in  March  1900. 
This  organism  had  repeatedly  caused  rheumatic  fever  in  rabbits, 


FIG.  58 

Experimental  rheumatic  endocarditis  ("simple'")  in  a  rabbit,  pro- 
duced by  intravenous  inoculation  of  the  diplococcus.  The  heart 
on  the  left  side  is  normal.  On  the  right  side  minute  vegetations  are 
seen  immediately  in  front  of  the  glass  rod;  their  minute  size  and  the 
absence  of  colour-contrast  makes  their  reproduction  by  ordinary 
photography  exceedingly  difficult. 


FIG.  59 

Heart   of  a  rabbit.     Left    auricle   and  ventricle   opened,   showing 

extensive  malignant  endocarditis  of  the  mitral  valve.     The  lesion 

was    the   result   of   intravenous   inoculation  with   the   Diplococcus 

rheumaticus. 


FIG.  60 


The  heart  of  a  rabbit.  The  left  auricle  and  ventricle  are  opened  and 
a  glass  rod  passed  under  two  small  vegetations  intermediate  in  size 
between  those  occurring  in  "simple"  and  "malignant"  endocarditis. 


STUDY  OF  MALIGNANT  ENDOCARDITIS        199 

and  two  specimens  of  simple  endocarditis  caused  by  it  are 
shown  among  the  macroscopic  specimens. 

For  some  months  the  organism  had  been  kept  growing 
in  the  acid  milk  medium,  but  it  had  not  of  late  been  passed 
through  an  animal,  and  we  were  doubtful  whether  it  had  not 
completely  lost  all  virulence. 

The  organism  was  transferred  to  blood  agar  tubes  in  the 
usual  manner,  and  an  exceptionally  large  amount  used  for 
inoculation. 

The  temperature  upon  the  next  day  was  1030  F.,  but  until 
the  fourteenth  day  we  noticed  no  change  at  all,  and  then 
we  found  the  heart  very  excited.  This  in  a  rabbit  is  not 
a  reliable  sign  of  cardiac  disease,  and  as  there  was  no  murmur 
we  somewhat  hastily  concluded  that  there  was  no  result  to 
be  expected.  The  animal  was  found  dead  on  the  nineteenth 
day. 

The  necropsy  made  the  cause  of  death  quite  clear.  The 
heart  was  large  and  the  cavity  of  the  left  ventricle  dilated. 
Vegetative  endocarditis  of  the  aortic  valve  had  practically 
closed  the  lumen  of  the  aorta,  and  the  aortic  ring  was  thickened. 
Minute  beads  were  found  fringing  the  mitral  valve,  and  its 
aortic  cusp  was  thickened  by  previous  endocarditis. 

From  the  aortic  vegetations  the  diplococcus  was  isolated, 
and  was  demonstrated  in  the  sections  of  the  valve.  There 
were  no  infarcts.  It  must,  we  think,  be  allowed  that  this 
was  a  very  remarkable  and  suggestive  result. 

Two  macroscopic  specimens  of  rabbits'  hearts  are  also 
shown,  one  resulting  from  an  injection  with  the  Diplococcus 
rheumaticus,  and  one  from  the  diplococcus  obtained  from 
a  case  of  malignant  endocarditis,  which  illustrate  the  tran- 
sitional phases  of  the  endocarditis,  and  also  a  third  specimen 
showing  primary  malignant  tricuspid  endocarditis  produced 
by  the  diplococcus  of  rheumatic  fever. 

The  remainder  of  the  series  of  experimental  investigations 
we  must  record  very  briefly.  These  investigations  were  made 
with  the  Streptococcus  pyogenes,  and  emphasise,  we  believe, 
the  salient  points  of  our  previous  results. 

Upon  two  occasions  virulent  cultures  of  the  Streptococcus 
pyogenes  obtained  from  a  case  of  puerperal  fever  were  supplied 
to  us  from  the  Jenner  Institute.  The  virulence  had  been 
increased  by  passing  the  organism  through  a  series  of  rabbits, 


200         STUDY  OF  MALIGNANT  ENDOCARDITIS 

and  the  cultures  that  we  received  may  be  looked  upon  as 
characteristic  of  the  virulent  Streptococcus  pyogenes. 

We  treated  this  micro-organism  in  the  same  way  that  we 
have  the  Diplococcus  rheumaticus,  that  is,  transferred  it  first 
to  the  acid  medium,  and  thence  to  blood  agar.  The  only 
difference  in  detail  was  the  use  for  inoculation  of  a  small  part 
of  the  growth  from  one  tube  instead  of  the  growth  from  some 
four  or  six  tubes.  With  such  a  small  quantity  as  this,  in  our 
experience,  no  result  is  obtained  with  the  diplococcus  of 
rheumatic  fever. 

The  rabbits  died  in  every  instance  within  twenty-four 
hours  of  inoculation.  The  post-mortem  appearances  differed 
widely  from  those  which  we  have  previously  described. 
There  were  haemorrhages  from  the  mucous  surfaces.  The 
blood  was  fluid,  the  spleen  large,  dark  and  soft,  the  kidneys 
pale  and  extremely  friable.  There  were  no  local  lesions, 
such  as  arthritis  or  endocarditis.  Microscopic  examination 
of  the  organs  showed  great  numbers  of  streptococci  in  the 
blood  capillaries  and  tissues. 

On  each  occasion  this  condition  of  septicaemia  resulted, 
and  although  we  cultivated  the  streptococcus  for  a  week 
in  the  acid  medium  (a  medium  which  is  not  considered  to  be 
a  favourable  one),  the  result  on  inoculation  was  the  same. 

It  may  be  objected  to  these  results  that  the  virulence  of 
the  streptococcus  had  been  artificially  raised,  and  that  they 
are  not  therefore  comparable  to  our  previous  investigations, 
but  this  objection  cannot  be  raised  against  the  next  case. 
A  woman  was  admitted  to  St.  Mary's  Hospital,  suffering 
from  septic  absorption  from  a  suppurative  phlebitis.  An 
operation  cured  her,  and  from  the  pus  the  Streptococcus  pyogenes 
was  isolated  and  cultivated  in  the  acid  medium,  and  then 
transferred  to  blood  agar.  Intravenous  inoculation  of  a 
rabbit  resulted  in  death  within  twenty-four  hours  from  a 
condition  of  septicaemia  of  the  same  nature  as  that  which 
resulted  from  the  streptococcus  sent  to  us  from  the  Jenner 
Institute. 

The  last  experiment  was  made  with  a  streptococcus  isolated 
from  the  pus  of  a  suppurative  pericarditis.  The  patient,  a 
boy,  had  died  from  a  streptococcus  pyaemia,  the  result  of  a 
punctured  wound  of  the  right  knee-joint. 

The  same  procedure  was  adopted  as  before,  and  on  this 


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STUDY  OF  MALIGNANT  ENDOCARDITIS        2oi 

occasion  the  rabbit  lived  for  five  days,  during  which  time 
arthritis  of  the  right  carpal  joint  developed. 

The  post-mortem  showed  purulent  arthritis,  small  abscesses 
in  the  liver  and  both  lungs,  a  clear  exudation  in  the  pericardium, 
and  a  fibrino-cellular  exudation  in  the  pleurae.  There  was  no 
endocarditis. 

These  investigations  with  the  Streptococcus  Pyogenes  serve 
to  show  more  distinctly  the  definite  character  of  the  results 
we  have  obtained  with  the  diplococcus  of  rheumatic  fever 
and  the  diplococcus  isolated  from  certain  cases  of  malignant 
endocarditis.  We  do  not  pretend  for  a  moment  that  they 
settle  the  question  of  the  relation  of  these  various  processes 
to  one  another,  but  they  demonstrate  that,  as  in  man,  charac- 
teristic rheumatic  fever  and  this  type  of  malignant  endocarditis 
on  the  one  hand  and  pyaemia  and  septicaemia  from  the 
Streptococcus  pyogenes  on  the  other  are  different  conditions, 
and  suggest  that  there  must  be  some  very  definite  reason  for 
such  differences. 

These  clinical  cases,  the  experimental  investigations,  and 
our  specimens  show,  we  believe  : 

Firstly,  that  the  probability  that  some  of  these  cases  of 
malignant  endocarditis  are  rheumatic  is  not  contrary  to 
clinical  experience. 

Secondly,  that  a  diplococcus  is  the  cause  of  some  of  these 
cases  of  malignant  endocarditis. 

Thirdly,  that  this  diplococcus  will  reproduce  in  rabbits 
malignant  endocarditis,  and  also  a  condition  we  consider 
to  be  rheumatic  fever. 

Fourthly,  that  the  Diplococcus  rheumaticus  will  produce 
malignant  endocarditis. 

(b)  Histology 

The  minute  anatomy  of  the  two  conditions  is  the  next 
consideration. 

If  a1  necropsy  is  made  upon  a  characteristic  case  of  rheumatic 
fever  and  upon  a  case  of  malignant  endocarditis  of  the  type 
under  consideration,  the  most  striking  feature  in  which  they 
differ  is  found  to  be  the  condition  of  the  damaged  cardiac  valves. 

In  acute  rheumatism  there  are  minute  vegetations,  in 
malignant  endocarditis  there  are,  as  a  rule,  large  exuberant 
masses,  with  possibly  also  ulceration  of  the  valve  substance 


202        STUDY  OF  MALIGNANT  ENDOCARDITIS 

and  rupture  of  chordae  tendineae.  Yet  these  large  vegeta- 
tions, save  in  one  respect,  do  not  differ  in  their  microscopic 
structure  from  the  minute  ones.  There  is  the  same  necrosis,  the 
same  cell  infiltration,  the  same  swelling  of  the  connective  tissue. 

If  a  careful  search  is  made  in  the  damaged  valve  of  rheu- 
matic fever,  the  diplococci  may  be  found  in  regions  where 
the  process  has  not  reached  the  limit  of  necrosis  though  the 
search  is  not  easy  because  the  fibrous  framework  of  the  valve 
is  not  an  easy  structure  to  examine  minutely.  If  search  is 
made  in  the  necrotic  part  of  the  vegetation,  all  attempt  to 
demonstrate  the  micro-organisms  may  and  probably  will  be 
met  with  failure  ;  they  have  been  for  the  most  part  destroyed. 
But  in  malignant  endocarditis  they  are  found  in  masses, 
sometimes  fringing  the  free  edge  of  the  vegetation,  sometimes 
buried  in  the  necrotic  tissue. 

This  then,  we  believe,  is  the  essential  difference  in  the 
morbid  anatomy  of  the  two  conditions.  Hence  it  is  that 
in  rheumatic  fever,  death  does  not  occur  from  acute  endo- 
carditis but  from  peri-  and  myo-carditis,  whilst  in  malignant 
endocarditis  death  occurs  almost  invariably  from  endo- 
carditis and  its  secondary  results  ;  though  occasionally 
during  the  illness,  sometimes  within  the  last  few  days  of  life, 
pericarditis  may  develop.  Hence  it  is  that  numerous  white 
infarcts  occur  in  the  malignant  form,  and  are  exceptional 
in  the  simple.  The  white  infarcts  need  no  detached  clot 
or  fragment  of  vegetation  for  their  formation,  it  is  sufficient 
that  a  considerable  mass  of  the  micro-organisms  be  carried 
to  the  spot,  and  there  set  up  by  their  poisonous  action  the 
phenomenon  of  coagulation  necrosis.  Upon  innumerable 
occasions  these  organisms,  which  grow  so  vigorously  in  the 
vegetation,  are  scattered  in  every  direction  by  the  blood 
stream,  and  give  rise  to  the  irregular  fever,  the  sweating, 
the  prostration,  and  wasting.  In  the  heart  the  process  steadily 
advances,  but  it  by  no  means  follows,  and  indeed  does  not 
follow,  that  the  secondary  foci  in  the  various  viscera  will  also 
of  necessity  steadily  progress.  The  place  of  election  in  this 
disease  is  the  heart,  and  no  one  can  seriously  doubt  that 
the  chemistry  of  each  particular  organ  of  the  body  must 
be  in  some  measure  peculiar,  and  it  is  not  strange  that  while 
the  process  is  spreading  in  the  heart  an  infarct  in  the  kidney, 
for  example,  may  be  healing. 


FIG.  63 

Section  -through  the  mitral  valve  (human),  from  a  case  of  rheumatic  fever  and  chorea. 

Numerous  diplococci  were  present  in  the  tissues.      Masses  of  diplococci  were  also  present 

in  the  cerebral  cortex  (vide  Fig.  64)  (Zeiss,  obj.  TV,  oc.  3).     The  vegetations  were  minute. 


STUDY  OF  MALIGNANT  ENDOCARDITIS  203 

The  clinical  distinction  between  a  characteristic  rheu- 
matic fever  and  malignant  endocarditis  is  wide,  and  the 
difference  in  the  vegetations  in  the  two  conditions  is  equally 
wide,  but  just  as  the  two  clinical  conditions  merge  the  one 
into  the  other,  so,  too,  do  these  vegetations.  In  some  cases 
of  rheumatic  fever  there  may  be  many  diplococci  in  the  valves. 
In  some  cases  of  malignant  endocarditis  the  vast  majority 
of  the  micro-organisms  are  destroyed.  The  first  represent 
cases  of  rheumatic  fever,  which  toward  the  end  approach 
the  type  of  malignant  endocarditis  ;  the  second  represent 
those  cases  of  subacute  malignant  endocarditis  of  long  duration 
in  which  the  virulence  appears  to  be  low  in  intensity,  but 
persistent  in  character. 

There  does  not  appear  to  us  to  be  any  essential  difference 
in  the  morbid  anatomy  of  the  two  conditions  other  than  this, 
that  for  some  occult  reason  the  micro-organism  in  the  malignant 
type,  instead  of  being  destroyed  in  the  vegetation,  survives 
and  multiplies.  It  also  seems  unlikely  to  us  that  the  organisms 
select  a  previously  damaged  valve — the  results  of  experiment 
indeed,  decided  against  this  ;  it  is  more  probable  that  there 
is  in  this  type,  as  in  rheumatic  fever,  that  same  tendency 
for  the  diplococci  to  attack  the  cardiac  valves,  and  that 
damaged  valves  from  lack  of  full  power  of  resistance  permit 
the  rapid  and  continual  growth  of  the  micro-organisms,  and 
in  this  way  predispose  to  the  malignant  type  of  the  disease. 

(c)  Bacteriological  Details 

To  turn  now  to  some  of  the  bacteriological  details.  We 
have  no  knowledge  of  the  occurrence  of  the  diplococcus  we 
have  isolated  from  these  cases  of  malignant  endocarditis 
outside  the  body,  except  in  so  far  as  we  have  studied  it  in 
culture.  In  the  body  it  is  present  in  the  local  lesions  which 
characterise  the  disease,  and  in  these  situations  it  may  be 
discovered  by  staining  sections  of  those  morbid  structures  with 
appropriate  dyes,  though  more  readily  still  by  treating  films 
made  from  scrapings  of  these  tissues. 

The  organism  is  stained  best  by  the  aniline  dyes,  but  in 
our  experience,  though  it  stains  by  Gram's  method,  it  does 
not  retain  the  stain  with  tenacity.  It  may  be  present  in 
the  vegetations  upon  the  cardiac  valves  in  enormous  numbers 


204        STUDY  OF  MALIGNANT  ENDOCARDITIS 

where  it  can  be  seen  in  the  substance  of  the  vegetation,  and  also 
in  large  masses  in  direct  contact  with  the  blood  stream. 

In  this  situation  it  is  present  as  a  minute  diplococcus, 
measuring  0.5^  or  even  less  in  diameter.  We  have  isolated 
it  in  pure  culture  by  the  incubation  of  scrapings  of  the  vege- 
tation in  a  mixture  of  bouillon  and  milk  slightly  acidified 
with  lactic  acid,  a  medium  such  as  we  used  for  isolating  the 
diplococcus  from  cases  of  rheumatic  fever.  When  cultivated 
in  this  manner  it  resembled  very  closely  the  latter  organism, 
though  it  is  slightly  smaller,  and  may  grow  in  longer  chains 
in  fluid  media,  and  form  more  definite  masses  upon  the  solid 
ones.  Such  differences  as  these,  we  believe,  can  be  explained 
by  its  more  rapid  growth. 

In  sub-cultures  made  upon  blood  agar,  which  is  very  suitable 
for  maintaining  its  virulence,  the  difference  between  these  two 
organisms  is  hardly  discernible.  Both  form  upon  this  medium 
discrete  colonies  of  minute  size,  the  smaller  and  younger  of 
which  are  translucent,  the  older  and  larger  opaque,  and  of  a 
yellowish  colour.  On  ordinary  media  the  growths  of  the  two 
organisms  are  strikingly  similar.  Thus  in  bouillon  they  form 
a  slightly  granular  deposit  on  the  sides  and  bottom  of  the  tube, 
while  the  supernatant  fluid  remains  clear.  On  gelatine  both 
form  discrete  non-liquefying  colonies,  but  these  media  are  not 
suitable  for  its  growth. 

Both  these  organisms  coagulate  the  milk  medium,  forming 
a  firm  coagulum,  but  the  diplococcus  from  the  malignant 
type  the  more  rapidly.  By  both,  alkaline  media  arc  rendered 
very  distinctly  acid. 

This  acid-producing  property  is  a  well-known  feature  in 
the  growth  of  many  bacteria.  Dr.  Sidney  Martin,  in  his 
important  researches  upon  the  poisons  of  infective  endo- 
carditis, attributed  this  to  a  non-proteid  body.  When  we 
recall  how  much  attention  has  been  directed  to  the  possibility 
of  some  acid-producing  process  in  the  metabolism  of  rheumatic 
affections,  and  when  we  bear  in  mind  the  wide-spread  belief 
in  the  value  of  treatment  by  alkalis,  we  are  led  to  wonder 
whether  sufficient  attention  has  been  given  by  clinicians 
to  this  result  of  bacterial  growth  in  rheumatic  and  gouty 
affections.  Is  it  not  possible  that  in  a  gouty  subject  an 
attack  of  gout  may  result  from  an  infection  with  these  acid- 
producing  bacteria  ? 


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FIG.    64 


Human  chorea.     Section  through  the  motor  cortex  showing  a  mass  of  diplococci  in  the 
neuroglia:  the  diplococci  were  also  demonstrated  in  the  mitral  valve.  (Zeiss,  obj.  TV,  oc.  3.) 


STUDY  OF  MALIGNANT  ENDOCARDITIS        205 

The  pathological  action  of  the  organism  was  studied  by 
isolating  it  in  the  milk  and  bouillon  medium  and  then  trans- 
ferring it  to  blood  agar.  Injections  were  made  directly  into 
the  circulation  of  rabbits  through  the  auricular  vein. 

III.  Concluding  Observations 

(a)   Upon  the  Specific  Nature  of  Rheumatic  Fever 

Finally,  it  remains  for  us  to  touch  very  briefly  upon  some 
of  the  considerations  that  arise  if  it  be  true  that  some  cases  of 
malignant  endocarditis  are  rheumatic  in  origin.  In  these 
considerations,  much  must  turn  upon  the  question  whether 
rheumatic  fever  is  a  specific  disease.  If  it  be  a  specific  disease 
the  processes  involved  must  be  specific,  and  the  problem  arises 
to  what  extent  this  specific  character  is  due  to  the  poisons  which 
are  formed  by  the  micro-organism,  and  to  what  extent  to  the 
peculiar  tissue  reactions.  As  knowledge  upon  this  problem  is 
gained,  the  mode  of  origin  of  the  malignant  type  may  become 
apparent.  Again,  whatever  the  nature  of  the  poisons  that  are 
formed  in  rheumatic  fever,  those  of  this  type  of  malignant  endo- 
carditis would  be  allied  to  them,  a  conclusion which,in  the  future, 
may  have  a  close  bearing  upon  the  treatment  of  the  disease. 

(b)   Upon  the  Relation  of  Septic  to  Rheumatic  Processes 

An  interesting  point  which  arises  from  this  question  of 
the  specific  nature  of  rheumatic  fever  is  the  relation  of  rheu- 
matic to  septic  processes.  Are  these  distinct  in  their  essence, 
or  is  rheumatic  fever  an  infection  with  attenuated  pyogenic 
micrococci,  as  Singer  3  maintains  ? 

We  have  been  compelled  to  differ  from  Singer  because 
we  have  isolated  only  one  organism  from  rheumatic  fever  ; 
nevertheless,  this  question  must  still  arise  in  a  slightly  modified 
form  thus  :  Is  this  diplococcus  we  have  isolated  the  attenuated 
Streptococcus  Pyogenes,  and  rheumatism  a  result  of  this  attenua- 
tion ?  In  reply  to  this  we  would  ask,  can  the  term  "  attenua- 
tion "  *be  applied  in  this  sense  ? 

Chemical  pathology  will,  we  suppose,  solve  this  question, 
and  meantime  we  are  driven  back  to  clinical  experience, 
and  ask  of  it  once  more,  is  rheumatic  fever  a  specific  disease  ? 
If  it  is,  the  diplococcus,  call  it  what  you  will,  must  be  to  this 
extent  specific,  that  it  has  produced  a  constant  disease.     It 


206        STUDY  OF  MALIGNANT  ENDOCARDITIS 

is  to  be  hoped  that  this  problem  of  the  relation  of  rheumatic 
to  septic  processes  will  be  solved  before  very  long,  and  if  the 
diplococcus  described  by  ourselves  and  others  proves  to  be  the 
only  cause  of  rheumatic  fever,  this  solution  will  mark  another 
step  in  the  progress  of  our  knowledge. 

(c)  The  Position  that  this  Type  of  Malignant  Endocarditis 

occupies 

Again,  if  the  two  processes,  rheumatic  and  septic,  are 
essentially  different,  then,  we  suppose,  mild  acute  rheumatism 
corresponds  to  the  milder  forms  of  pyaemia,  virulent  rheumatism 
to  severe  pyaemia  ;  this  form  of  endocarditis  to  malignant 
endocarditis  with  suppuration,  while  septicaemia  perhaps 
finds  a  parallel  in  some  cases  of  rheumatism  with  profound 
toxaemia. 

We  have  undertaken  some  investigations  into  this  subject — 
starting  from  the  assumption  that  the  micro-organisms 
isolated  from  distinct  types  of  rheumatic  and  septic  diseases 
should,  if  placed  under  the  same  conditions  out  of  the  body, 
produce  also  distinct  types  of  disease  in  susceptible  animals. 

Thus  from  rheumatic  fever,  puerperal  fever,  suppurative 
phlebitis,  pyaemia,  and  cellulitis,  we  have  isolated  the  orga- 
nisms, and  have  endeavoured,  as  far  as  possible,  to  maintain 
their  virulence  by  transferring  them  at  once  to  blood  agar. 
Rabbits  have  been  injected  with  these  cultures,  but  as  yet 
pyaemia  has  not  resulted  from  the  Diplococcus  rheumaticus, 
or  rheumatic  fever  from  the  pyogenic  organisms.  Triboulet 
records  the  same  experience.4  We  do  not  pretend  these 
investigations  are  by  any  means  sufficient  to  settle  this  question ; 
but  we  make  allusion  to  them  because  it  does  seem  an  important 
point  in  the  study  of  the  large  group  of  pathogenic  micrococci 
to  choose  typical  examples  of  the  disease  of  which  they  are 
thought  to  be  the  cause,  and  then  to  put  these  organisms 
to  the  test  of  experiment  under  similar  conditions,  rather 
than  to  deal  with  cultures,  the  virulence  of  which  has  been 
artificially  raised,  or  with  organisms  that  have  been  placed 
upon  various  media  far  removed  from  their  natural  soil. 

(d)  Local  Malignancy  in  other  Rheumatic  Manifestations 

To  the  assertion  that  these  cases  of  malignant  endocarditis 
are    rheumatic    the    fair    criticism   may  be   raised  that  such 


STUDY  OF  MALIGNANT  ENDOCARDITIS        207 

persistent  local  processes  should  be  met  with  also  in  other  of  the 
rheumatic  manifestations.  It  cannot  be  supposed  that  any 
lesion,  except  of  the  heart  or  great  blood-vessels,  would 
produce  the  same  condition  of  blood  infection  as  does  the 
malignant  endocarditis,  for  there  will  not  be  that  same  relation 
of  the  local  lesions  to  the  general  blood  stream. 

1.  Malignant  pericarditis.  Yet  it  is  well  recognised  that 
there  is  in  childhood  a  persistent  intractable  malignant  form 
of  pericarditis.  This  may  smoulder  on  for  months,  the  process 
throughout  being  a  repeated  local  pericarditis,  never  an  acute 
general  inflammation.  In  such  a  condition  as  this,  if  the 
organisms  in  the  pericardium  had  the  same  easy  access  to  the 
general  circulation  that  they  have  in  the  vegetation  of  a  valve, 
we  should  suspect  the  similar  character  of  the  two  conditions 
would  be  at  once  apparent. 

2.  Malignant  arthritis  and  rheumatoid  arthritis.  It  is 
probable,  too,  that  the  same  process  occurs  sometimes  in  the 
joints,  and  gives  rise  to  chronic  destructive  lesions  of  one  or 
more,  a  condition  included  in  the  disease  of  joints  known  as 
rheumatoid  arthritis.  Such  a  condition  of  the  joints  need 
not  react  to  treatment  by  salicylate  of  soda  any  more  than  do 
the  conditions  of  endocarditis  or  pericarditis. 

(e)  The  Insidious  Onset  of  Rheumatic  Fever. 

Another  criticism  of  the  investigation  that  may  be  raised 
from  the  clinical  side  is,  that  though  malignant  endocarditis 
and  rheumatic  fever  may  in  their  course  sometimes  resemble 
one  another,  their  modes  of  onset  are  widely  different.  The 
onset  of  rheumatic  fever,  it  may  be  said,  is  comparatively 
acute  ;  of  this  type  of  malignant  endocarditis  almost  invariably 
very  gradual. 

Rheumatic  fever,  no  doubt,  does  very  often  commence 
somewhat  acutely,  but  in  childhood  we  are  repeatedly  met 
with  the  history  that  before  the  definite  rheumatic  symptoms 
were  noticed  the  child  had  been  out  of  health,  was  becoming 
anaemic  and  irritable,  and  was  losing  flesh.  If  the  temperature 
is  taken  it  may  be  found  to  be  raised  during  this  period.  The 
onset  of  rheumatic  fever  is  then  often  insidious,  as  Sir  William 
Church  emphasised  in  his  article  upon  acute  rheumatism 
in  Professor  Clifford  Allbutt's  "  System  of  Medicine."  It 
appears  to  us  that  observations  in  every  direction  tend  to 


2o8         STUDY  OF  MALIGNANT  ENDOCARDITIS 

strengthen  the  view  that  this  diplococcus  may  live  for  long 
periods  in  the  body,  as  it  certainly  does  in  culture  outside  the 
body.  Possibly  it  may  remain  latent ;  often  it  produces 
indeterminate  symptoms,  and  finally  it  may  produce  charac- 
teristic svmptoms.  The  repeated  relapses  of  the  chronic 
types  of  rheumatic  fever  are  most  probably  to  be  explained  in 
this  resistance  of  the  micro-organism  to  complete  destruction. 
We  must  once  more  thank  Dr.  W.  B.  Cheadle  and  Dr. 
D.  B.  Lees  for  leave  to  make  use  of  their  clinical  cases.  It 
would  be  impossible,  if  it  were  not  for  this  assistance,  to 
collect  sufficient  data  for  the  generalisations  which  are  essential 
in  investigations  of  this  nature.  To  Mr.  H.  G.  Plimmer, 
Pathologist  to  St.  Mary's  Hospital,  we  must  also  again  express 
our  indebtedness. 

REFERENCES 

1  "  Ueber  die  maligne  (Xichtseptische)  Form  der  Endocarditis 
Rheumatica,"  Berliner  klinische  Wochenschrift,  1899,  No.  29,  p.  644. 

2  "  Ueber  den  Infectiosen-Charakter  und  den  Zusammenhang  von 
acuten  Gelenkrheumatismus  und  Chorea,"  Berliner  klinische  Wochen- 
schrift, 1899,  No.  29.  p.  638. 

3  "  Weitere  Erfahrungen  uber  die  Aetiologie  des  acuten  Gelenkrheu- 
matismus."  Wiener  klinischen  Wochenschrift.  Jahrgang  1901,  No.  20. 

4  "  Le  Rhumatisme  Articulaire  Aigu,"   1901. 


PAPER  NO.  XVI 

A  CONTRIBUTION  TO  THE  STUDY  OF 
RHEUMATIC  IRITIS 

(Reprinted  from  vol.  xxiii  of  the  Ophthalmological  Society's 
Transactions) 

This  paper  gives  a  short  account  of  the  experimental  production  of 
iritis  by  intravenous  inoculation  of  the  diplococcus,  and  considers  the 
bearing  of  the  results  upon  the  occurrence  of  rheumatic  iritis  in  man. 

Introductory 

Before  we  commence  this  paper  we  must  define  our 
position.  We  do  not  pretend  to  that  skilled  knowledge  of 
irido-cyclitis  which  would  be  asked  of  an  expert,  but  have 
— when  investigating  the  subject  of  rheumatic  fever — observed 
certain  facts  which  may.be  of  interest  to  ophthalmic  surgeons, 
and  which  in  this  spirit  we  bring  before  you  on  this  occasion. 

For  us  rheumatic  iritis  is  rather  an  incident  in  a  general 
infection  than  in  itself  a  disease,  and  for  our  purpose  it  matters 
little  whether  it  is  rare  or  frequent  in  its  occurrence.  The 
question,  as  it  presents  itself,  is  sufficiently  simple  :  Can  a 
micro-organism  which  is  a  cause  of  rheumatic  fever  produce 
iritis  as  it  does  endocarditis,  pericarditis,  arthritis,  pleuritis, 
and  subcutaneous  nodules  ? 

For  the  ophthalmic  surgeon  the  subject  is  much  more  com- 
plex, involving  points  in  treatment  and  refinements  in  diagnosis 
and  management  to  which  we  need  not  now  allude.  For 
him  jt  is  a  disease  of  first  importance  ;  for  us  it  is,  as  we  have 
said,  an  incident  in  a  general  infection. 

The   Clinical  Position  of  Acute  Rheumatic  Iritis 

Among  ophthalmic  surgeons  we  believe  there  is  some 
divergence   of  opinion  as  to  the   frequency  and   occurrence 

209  14 


210  A  CONTRIBUTION  TO  THE  STUDY 

of  acute  rheumatic  iritis,  though  there  appears  to  be  little 
doubt  that  it  is  a  rare,  but  not  unknown  event — a  statement 
which  we  would  venture  to  support  with  such  experience  as 
we  have  had  ourselves.  Further  support  of  its  rarity  was 
supplied  in  January  1903,  by  Macrae,  in  the  Journal  of  the 
American  Medical  Association,  who  noted  its  occurrence  only 
once  in  270  cases  of  rheumatic  fever. 

A  good  example   of  the  condition  was   published  in  the 
British  Medical  Journal  for  March  7,  1903,  by  Mr.  F.  C.  Forster, 
of  Lowestoft,  and  in  addition  Mr.  Forster  kindly  sent  us  in  a 
letter  some  further  details,  which  we  have  his  leave  to  quote. 
It  may  perhaps  be  remembered  that  it  was  the  case  of  a  girl, 
I2|  years  of  age,  who  developed,  after  a  definite  chill,  tonsillitis 
and  arthritis.     Then  followed  chorea,  and  later  iritis  of  the  right 
eye   and  endocarditis.     In  his  letter  Mr.   Forster  writes  as 
follows  :     "  The  iritis  came  on  very  suddenly  when  she  was 
recovering  from  chorea.     The  right  eye  alone  was  affected  ; 
the  pupil  was  altered  in  shape,  and  a  naturally  brown  eye 
assumed  a  yellow  tinge.  .  .  .  There  was  the  usual  marked 
congestion    (especially  circumcorneal),   with    great    pain  and 
photophobia  ;    the  pain  was  both  topical  and  supra-orbital. 
.  .  .  The  iritis  relapsed  twice,  and  I  feared  that  some  posterior 
synechise  would  eventually  lead  to  diminution  of  vision.  .  .  . 
Recovery  was  eventually  good.     Rheumatic  iritis,"  he  adds, 
"  is,  of  course,  not  common  in  children,  but  I  have  met  with 
few  more  typical  than  the  one  under  discussion.     Syphilis, 
gonorrhoea,  and  trauma  may  certainly  be  excluded  as  causes 
in  this  particular  case." 

This  seems  to  us  a  clear  example  of  acute  rheumatic  iritis 
of  unusual  severity.  Such  examples  as  we  have  seen  have 
been  very  transient. 

Among  those  who  are  opposed  to  the  acceptance  of  acute 
rheumatic  iritis,  much  importance  is  attached  to  the  gonor- 
rhceal  infection.  Even  if  this  may  have  occurred  some  years 
before,  they  attribute  an  iritis  of  a  rheumatic  type  to  that 
cause.  In  passing  we  would  venture  to  point  out  the  well- 
known  fact  that  rheumatic  symptoms  are  most  liable  to 
occur  in  those  subjects  of  gonorrhoea  who  have  suffered 
previously  from  rheumatic  fever  ;  also  that  the  diplococcus 
of  the  gonorrhceal  affection  was  one  of  the  earliest  known 
of  this  type  of  micro-organism,  and  its  recognition  established 


OF  RHEUMATIC  IRITIS  211 

in  text -books  on  hard  and  fast  lines,  which  with  more  mature 
experience  are  perhaps  a  little  too  hard  and  fast  ;  and,  lastly, 
that  the  rheumatic  infection  equally  as  much  as  the  gonorrhceal 
is  liable  to  lurk  in  the  system  for  long  periods.  Both  diseases 
may  theoretically  be  causes  of  iritis.  Both  linger  in  the 
system.  We  are  thus  in  agreement  with  Mr.  Lawford's 
opinion  as  expressed  at  the  British  Medical  Association 
meeting  in  August  1901,  on  the  imperfection  of  this  proof  of 
the  gonorrhceal  origin  of  many  cases  of  iritis. 

The  Object  of  the  Communication 

The  object  of  our  communication  is  to  show  that  acute 
iritis  may  result  in  rabbits  from  experimental  inoculations 
with  a  diplococcus  or  micrococcus  which  is  a  cause  of  rheumatic 
fever. 

Other  observers — for  example,  Birch-Hirschfeld — have  pro- 
duced septic  panophthalmitis  by  inoculations. from  cases  of 
septic  endocarditis,  but  in  our  two  cases  the  micro-organism 
was  isolated,  first,  from  a  case  of  ordinary  rheumatic  fever 
in  a  child,  and,  secondly,  from  a  case  of  malignant  endo- 
carditis of  rheumatic  origin,  and  in  neither  animal  did  there 
result  septic  panophthalmitis. 

The  cases  we  will  detail  immediately,  but  we  first  emphasise 
the  fact  that  these  inoculations  were  intravenous — into  the 
auricular  veins  of  rabbits, — and  not  local — into  the  eye.  Had 
they  resulted  from  local  inoculations  we  should  not  personally 
have  attached  any  importance  to  them. 

The  Investigation 

Case  i.  In  1899  a  boy  of  9  years,  who  was  suffering 
from  morbus  cordis,  developed,  while  under  observation, 
active  rheumatism — that  is  to  say,  arthritis,  pericarditis, 
and  subcutaneous  nodules.  Death  resulted  from  pericarditis. 
From^  the  pericardial  fluid,  which  was  clear  but  contained 
also  flakes  of  exudation,  minute  diplococci  were  isolated.  They 
were  also  demonstrated  in  films  of  the  pericardial  fluid,  in  which 
they  grew  in  chains.  The  necropsy  showed  the  usual  results  of 
rheumatic  fever  in  childhood — there  was  no  suppuration. 

The  first  rabbit  inoculated  intravenously  with  the  peri- 
cardial fluid  died  on  the  ninth  day  of  arthritis,  pericarditis, 


212  A  CONTRIBUTION  TO  THE  STUDY 

and  broncho-pneumonia.  The  second  died  on  the  twentieth 
day  with  arthritis  and  pericarditis.  The  third  recovered. 
The  fourth  was  killed  on  the  tenth  day,  and  suffered  from 
arthritis  and  mitral  endocarditis.  The  fifth  was  killed  on 
the  ninth  day,  and  suffered  from  pericarditis,  pleurisy,  endo- 
carditis, pneumonia,  and  arthritis.  The  sixth  developed 
choreiform  movements,  and  was  killed.  The  seventh  died  of 
malignant  endocarditis.  The  eighth  died,  on  the  tenth  day, 
of  pericarditis  and  endocarditis  with  an  infarct  in  the  left 
lung.  It  was  this  animal  that  developed  iritis  of  the  left  eye. 
The  ninth  developed  chronic  rheumatic  arthritis  ;  and  then 
we  lost  the  strain,  failing  to  recover  the  organisms  from  the 
exudation.  Thus  it  will  be  seen  that  of  a  series  of  nine  animals 
only  one  developed  iritis.  There  was  nothing  unusual  about 
the  inoculation,  but  the  animal  was  a  feeble  one.  On  the 
fifth  day  there  was  some  lacrymation  ;  this  continued  for  two 
days  and  then  followed  injection  of  the  conjunctival  vessels, 
discoloration  of  the  iris,  and  considerable  exudation  into  the 
anterior  chamber.  It  should  be  clearly  stated  that  the 
appearance  was  not  like  that  of  an  hypopyon,  and  after 
death  the  fluid  was  not  opaque  and  yellow,  but  a  little  cloudy, 
although,  as  will  be  seen,  it  contained  vast  numbers  of  the 
micro-organism.  The  condition  in  no  way  resembled  one 
of  septic  panophthalmitis.  It  was  an  easy  matter  to  grow 
the  micro-organism  again  from  the  fluid  in  the  anterior 
chamber,  and  it  showed  the  usual  characters.  The  next 
rabbit  inoculated  developed  chronic  arthritis. 

Under  the  three  microscopes  there  are  shown  : 

(i)  A  film  of  the  exudation. 

(2)  A  section  of  the  iris  under  a  low  power  showing  the 
exudation,  fibrino-cellular  in  character,  on  the  anterior  surface 
of  the  iris. 

(3)  The  same  under  a  high  power  showing  the  micrococci 
in  the  exudation. 

The  anterior  surface  of  the  iris,  after  removal,  was  seen 
to  be  dotted  over  with  small,  raised,  white  areas. 

The  minute  description  of  the  changes  is  given  with  the 
drawings  placed  beside  the  microscopes. 

Since  that  investigation  we  have  repeatedly  studied  the 
illness  produced  in  rabbits  by  the  injection  of  this  micro- 
coccus,  and  although  we   have   from  time   to   time   noticed 


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OF  RHEUMATIC  IRITIS  213 

lacrymation  and  slight  conjunctivitis,  we  have  only  once  met 
with  iritis  again,  and  that  with  a  culture  obtained  from  the 
malignant  type  of  rheumatic  endocarditis. 

Case  2.  A  boy  aged  13  years,  in  December  1900,  was 
admitted  under  Dr.  Lees  to  St.  Mary's  Hospital  for  heart 
disease.  He  had  suffered  two  years  before  from  an  attack 
of  rheumatic  fever.  The  present  illness  had  commenced 
insidiously.  Mitral  and  aortic  disease  were  discovered  ; 
the  boy  went  from  bad  to  worse,  and  died  rather  unexpectedly 
in  January  1901. 

General  pericardial  adhesion,  malignant  mitral  and  aortic 
endocarditis,  and  a  splenic  infarction  were  found.  There  was 
no  suppuration.  Two  hours  after  death  we  isolated  from 
the  cardiac  valves  a  minute  diplococcus. 

Intravenous  inoculations  were  made. 
Rabbit  No.  1  died  of  malignant  mitral  endocarditis  with  iritis. 
,,     ,,     2      ,,       pericarditis  and  endocarditis. 
,,     ,,     3      ,,       pericarditis  and  endocarditis. 
,,     ,,     4      „       pericarditis. 
,,     ,,     5  recovered. 

It  is  remarkable  and  interesting  that  in  a  considerable 
number  of  investigations  we  have  only  met  with  iritis  twice  ; 
and  that  Fritz  Meyer,  who  has  made  extensive  experiments 
with  animals  with  a  smilar  organism,  does  not  mention  its 
occurrence.  Nor,  to  our  knowledge,  have  Dr.  Ainley  Walker 
and  Dr.  Beaton  met  with  it.  It  must,  we  think,  be  a  rare 
occurrence,  as  in  man. 

There  is  still  a  great  gap  in  our  knowledge.  For  no  one, 
so  far  as  we  are  aware,  has  isolated  this  organism  from  a 
case  of  rheumatic  iritis  in  man  and  produced  rheumatic  fever 
in  animals.  We  have  waited  in  vain  for  such  an  opportunity 
for  three  years,  and  bring  this  forward  in  the  hope  that  some 
one  may  complete  the  chain  of  evidence. 


PAPER  NO.  XVII 

ON  THE  RELATION  OF  THE  STAPHYLO- 
COCCUS PYOGENES  AUREUS  TO  RHEU- 
MATIC FEVER 

By  Dr.  F.  J.  POYNTON  and  Dr.  W.  V.  SHAW. 

(Reprinted  from  the  Transactions  of  the  Pathological  Society  of  London, 

1904) 

Dr.  Vernon  Shaw,  who  had  previously  demonstrated  the  experimental 
production  of  acute  rheumatism  in  monkeys,  collaborated  in  this 
paper,  which  deals  primarily  with  a  statement  that  has  been  made 
to  the  effect  that  acute  rheumatism  is  an  attenuated  pycemia.  A  frankly 
Pycemic  type  of  infection  is  chosen  in  the  staphylococcal  pyogenes 
aureus,  and  this  micrococcus  and  the  results  it  produces  in  man, 
monkeys,  and  rabbits  compared  with  those  produced  by  the  diplococcus 
of  acute  rheumatism.  An  attempt  is  made  in  the  second  part  of 
this  paper  to  investigate  multiple  infections,  a  line  of  investigation 
which  in  the  future  promises  to  throw  fresh  light  upon  the  problem  of 
rheumatism  and  its  relation  to  other  micrococcal  infections. 

The  object  of  this  paper  is  to  continue  the  series  of  investi- 
gations which  have  been  made  in  recent  years  upon  the  infec- 
tive origin  of  rheumatic  fever,  and  to  uphold  the  view  that  the 
disease,  is,  in  all  probability,  a  special  one,  for  the  clinical 
entity  has  already  been  established  by  the  careful  investigations 
of  experienced  observers.  We  rely  for  our  evidence  upon 
clinical,  pathological,  and  experimental  studies,  firmly  believing 
that  it  is  only  by  a  broad  survey  of  the  question  that  the 
problems  of  rheumatic  fever  can  be  solved.  It  is,  we  believe, 
essential  to  place  the  bacteriological  and  experimental  results 
side  by  side  with  the  clinical  course  of  the  disease  in  man,  in 
order  to  avoid  the  danger  of  becoming  involved  in  side  issues 
or  half-truths,  and  in  support  of  this  we  would  instance  one 
example,  that  of  endocarditis.     All  must  admit  that  this  is  an 

214 


FIG.   67 

Experimental  rheumatic-  arthritis.  Film  from  exudation  in  the  knee-joint 
of  a  monkey  intravenously  injected  with  the  diplococcus.  (Zeiss,  J„,  oc.  4.) 
The  animal  had  recovered  from  a  previous  mild  attack  of  arthritis,  but  suc- 
cumbed to  a  second  culture,  taken  two  hours  after  death,  from  a  child 
dead  of  rheumatic  fever  :  death  occurred  on  the  fifth  day  from  mitral  and  aortic 
endocarditis  with  myocarditis. 


THE  STAPHYLOCOCCUS  AND  RHEUMATIC  FEVER  215 

important  result  of  rheumatic  fever,  and  a  direct  consequence 
of  the  disease,  for  there  is  no  trustworthy  evidence  to  point 
to  it  as  an  indirect  or  secondary  result.  All  must  admit,  too, 
that  the  allied  infections,  the  pneumococcal,  the  stapylococcal, 
gonococcal,  and  streptococcal  (pyogenes  so  called),  may  also 
in  some  instances  produce  endocarditis,  but  the  series  of 
events,  and  the  course  and  history  of  the  cases  in  any  of  these 
infections,  are  different  from  the  accepted  course  of  a  true 
rheumatism.  Again,  until  recently,  experimental  endocarditis 
was  a  rare  occurrence,  but  now  it  is  a  frequent  one,  for  this 
reason,  that  a  diplococcus  obtained  from  the  damaged  valves 
in  that  very  disease,  rheumatic  fever,  which  above  all  causes 
endocarditis,  possesses  the  power  of  producing  experimental 
endocarditis,  with  remarkable  constancy.  Yet  in  spite  of 
this  there  are  some  investigators  who  draw  the  conclusion 
that  experiment  in  this  matter  is  useless,  because  they  have 
found,  naturally  enough,  that  the  other  micrococci  will  also 
sometimes  produce  endocarditis  in  animals  as  they  will  in 
man.  With  that  conclusion  we  do  not  agree.  Another 
inference  that  has  been  drawn  is  that  because  some  of  these 
other  micrococci  have  produced  endocarditis,  they  are  also 
capable  of  producing  rheumatic  fever.  We  believe  that  also 
is  a  dangerous  inference,  and  not  warranted  by  a  true  and 
careful  consideration  of  the  facts.  Neither  do  we  believe 
that  rheumatic  fever  can  be  considered  an  example  of  an 
attenuated  pyaemia  in  a  commonly  accepted  meaning  of 
the  term  pyaemia. 

At  this  point  we  wish  to  put  before  you  very  definitely  our 
view  on  this  question  of  rheumatic  fever  considered  as  an 
attenuated  pyaemia.  If  those  who  hold  this  view  imply  by 
it  that  rheumatic  fever  is  a  disease  of  the  pyaemic  type  in  that 
it  shows  various  local  lesions,  which  contain  within  themselves 
at  one  time  or  another  the  infective  agent,  and  further  if  they 
wish  to  emphasise  that  these  lesions  tend  to  take  as  a  rule 
a  benign  course,  then  we  also  are  quite  in  accord  with  that 
view  which  has  been  taught  us  by  earlier  investigators.  But 
if  they  wish  to  imply,  as  many  do,  that  any  disease  of  the 
pyaemic  type,  that  is  any  disease  which  causes  multiple 
abscesses,  will,  when  of  a  mild  type,  produce  rheumatic  fever, 
we  are  opposed  to  them.  They  then  clearly  hold  that  the 
disease  is  not  an  entity,  while  we  hold  that  it  is  as  definite  an 


216        RELATION  OF  THE  STAPHYLOCOCCUS 

entity  as  tuberculosis.  If  the  view  be  accepted  that  rheumatic 
fever  is  not  an  entity  but  is  an  attenuated  pyaemia,  it  should 
follow  that  the  Staphylococcus  aureus,  itself  a  most  important 
cause  of  pyaemia  in  man,  should  also  be  in  its  attenuated  state 
a  frequent  cause  of  rheumatic  fever.  But  we  shall  attempt 
to  show  that  in  our  experience  far  from  the  Staphylo- 
coccus aureus  b^ing  a  frequent  cause  of  rheumatic  fever,  it  is 
not  a  cause  of  this  disease  at  all,  and  that  therefore  the  vague 
conception  of  rheumatic  fever  as  an  attenuated  pyaemia 
must  be  abandoned  so  far  as  the  Staphylococcus  aureus  is 
concerned. 

We  take  as  our  type  of  rheumatic  fever  the  disease  as  it 
occurs  in  childhood  and  in  the  young  adult,  and  rely  entirely 
on  fatal  cases  which  post-mortem  examinations  have  confirmed 
as  the  true  disease.  In  this  way  alone  can  we  hope  to  start 
from  some  point  of  agreement,  for  we  believe  that  no  one  will 
dispute  that  the  post-mortem  evidences  of  rheumatic  fever  are 
very  definite  ones,  and  on  the  other  hand,  that  if  there  is  not 
a  post-mortem  examination  it  is  always  open  to  any  objector 
to  question  the  diagnosis. 

It  is  first  essential  for  us  to  show  that  it  is  possible  with 
reasonable  care  to  distinguish  the  two  micro-organisms,  the 
Staphylococcus  aureus  and  Diplococcus  rhcumaticus,  as  the 
following  data  will  show. 

A.  The  Staphylococcus  pyogenes  aureus  is  about  i.O/x  in 
diameter,  and  grows  in  irregular  clumps.  It  is  usually  a 
micrococcus. 

The  Diplococcus  rhcumaticus  measures  about  0.5^  in  diameter, 
and  grows  in  masses  on  solid  media  and  in  chains  in  liquid 
m  dia.     It  is  usually  a  diplococcus. 

b.  The  staphylococcus  stains  well  by  Gram's  method. 
The  diplococcus  stains  feebly  by  Gram's  method. 

c.  The  staphylococcus  liquefies  gelatine. 
The  diplococcus  does  not  liquefy  gelatine. 

d.  The  staphylococcus  grows  freely  on  agar,  forming  a 
smooth,  white,  shining,  opaque  layer,  which  on  exposure 
becomes  of  a  deep  yellow  colour. 

The  diplococcus  grows  (but  not  freely)  on  agar,  forming 
minute,  discrete,  white,  slightly  opaque  colonies,  and  there 
is  no  development  of  colour. 

The  same  is  true  of  litmus  agar. 


FIG.   68 

Experimental  arthritis.      A  film  from  the  exudation  in  the  knee-joint  of  a  rabbit  dead 

from  the  intravenous  injection  of  the  Staphylococcus  aureus.     The  animal  died  of  pyaemia 

on  the  third  day.     (Zeiss,  obj.  TV,  oc.  i.) 


PYOGENES  AUREUS  TO  RHEUMATIC  FEVER    217 

e.  The  staphylococcus  growing  in  bouillon  makes  the  fluid 
at  first  turbid,  and  later  clear  with  a  yellowish  sediment. 

The  diplococcus  in  the  same  medium  forms  a  flocculent  white 
precipitate  leaving  the  supernatant  fluid  clear. 

f.  The  staphylococcus  upon  potato  gives  an  abundant  yellow 
growth. 

The  diplococcus  grows  feebly  upon  the  same  medium, 
forming  minute  discrete  colourless  colonies. 

G.  The  staphylococcus  grows  well  and  freely  upon  blood 
agar.  After  twenty-four  hours  at  370  C.  it  appears  as  an 
opaque  yellowish  paint-like  growth  spreading  out  from  the 
track  of  inoculation.  On  further  incubation  it  grows  into 
the  medium,  producing  a  yellowish  brown  discoloration. 

The  diplococcus  grows  well  on  blood  agar.  After  twenty- 
four  hours'  incubation  the  colonies  appear  as  distinct,  clear, 
and  almost  colourless  growths  along  the  track  of  inoculation 
On  further  incubation  the  colonies  increase  in  size,  but  do  not 
form  a  continuous  film  unless  present  in  great  numbers.  In  time 
they  produce  a  change  of  colour,  and  the  red  brown  of  the 
blood  agar  is  changed  into  a  yellow  brown  where  the  micro- 
cocci grow  down  into  the  medium.  The  alteration  is  very 
similar  to  that  produced  by  the  pneumococcus. 

h.  Both  micro-organisms  grow  in  alkaline  litmus  milk,  but 
the  diplococcus  usually  produces  more  acid,  and  a  firm  clot  ;  the 
Staphylococcus  aureus  less  acid  and  a  looser  clot. 

In  1901  Triboulet  and  Coyon  showed  that  the  diplococcus 
produced  formic  acid  in  nitrogenous  media,  and  acetic  acid  in 
milk.  In  this  treatise1  they  give  a  careful  account  of  various 
acids  which  they  have  found  during  the  growth  of  the  micro- 
organism. The  production  of  formic  acid  has  been  fully  con- 
firmed by  Dr.  Ainley  Walker  and  Mr.  Ryffel.2  And  for  us  Mr. 
George  Berger  of  King's  College,  Cambridge,  has  demonstrated 
that  acetic  acid  is  especially  formed  in  the  milk  medium, 
confirming  again  the  observations  of  Triboulet  and  Coyon. 

It  is  clear  then  that  with  care  these  two  micro-organisms 
can  be  differentiated  from  one  another. 

We  next  come  to  these  all-important  questions  :  Is  the 
Staphylococcus  aureus  an  organism  which  is  present  in  cases  of 
undoubted  rheumatic  fever,  and  can  it  be  isolated  from  the 
local  lesions  ?  Our  experiences  and  those  of  Dr.  Paine  have 
been  very  definite,  for  we  have  not  found  this  micro-organism, 


2i8         RELATION  OF  THE  STAPHYLOCOCCUS 

and  although  we  do  not  pretend  that  we  have  always  obtained 
pure  cultures  in  our  investigations,  yet  when  we  failed  to  do  so 
we  did  not  find  the  Staphylococcus  aureus  as  the  cause  of  the 
mixed  culture.  Needless  to  say,  we  attach  great  importance 
to  this  evidence,  which  appears  to  us  to  have  a  vital  bearing 
on  the  pathogenesis  of  rheumatic  fever. 

Further,  though  each  one  of  us  has  isolated  the  Staphylococcus 
aureus  from  the  human  tissues,  the  conditions  we  have  found  in 
such  cases  were  not  to  be  confused  with  those  of  rheumatic  fever, 
when  it  was  possible  to  make  the  investigation  complete,  but  if 
the  investigation  is  incomplete  it  is  easy  enough  to  fall  into 
error.  It  is,  for  example,  within  the  experience  of  all  that  the 
Staphylococcus  aureus  may  cause  an  arthritis  or  pleurisy,  which 
need  not  reach  the  stage  of  suppuration,  and  which  clinically 
cannot  be  distinguished  from  the  rheumatic  inflammation. 
So  also  the  tubercular  infection  may  sometimes  cause  these 
same  fleeting  inflammations. 

But  we  do  not  call  these  conditions  "  pseudo-rheumatism," 
much  less  rheumatic  fever.  Again,  because  we  usually  meet 
with  staphylococcic  arthritis  in  the  suppurative  stage,  and 
rheumatic  arthritis  in  the  non-suppurative  stage,  we  do  not 
think  it  correct  to  argue  that  the  rheumatic  arthritis  is  an 
attenuated  variety  of  the  staphylococcal.  The  tubercular, 
pneumococcic,  staphylococcic,  and  other  infections  show 
different  grades  of  virulence  and  these  assist  in  producing  the 
differences  in  the  clinical  course  of  the  diseases  which  result. 
We  expect  the  same  to  occur  with  the  rheumatic  infection, 
and  believe  that  it  does  occur,  although  its  recognition  is 
obscured  by  the  use  of  such  adjectives  as  rheumatoid,  septic, 
or  malignant.  All  the  great  infectious  diseases  show  their 
different  types  of  virulence,  but  for  some  reason  or  other  when 
this  power  is  claimed  for  the  rheumatic,  it  is  often  objected 
that  rheumatic  fever  is  not  really  a  disease  at  all  but  only  a 
peculiar  reaction  to  many  infections. 

Our  position  is  not  based  on  mere  theory.  There  is  the 
evidence  of  clinical  observation,  such  as  Dr.  Paine  and  Dr. 
Poynton  put  forward  in  a  paper  upon  malignant  endocarditis, 
published  in  the  Medico-Chirurgical  Transactions  in  1902. 
There  is  also  the  experimental  proof  put  forward  upon  that 
occasion.  We  will  give  a  further  experimental  proof  with 
the  diplococcus  kindly  sent  to  one  of  us  (W.  V.  S.)  by  Professor 


FIG.   69 

Heart  of  a  monkey.  The  left  ventricle  is  laid 
open  and  the  mitral  and  aortic  valves  exposed. 
Vegetations  of  considerable  size  are  seen  on  each 
segment  of  the  aortic  valve.  Minute  vegetations 
are  also  present  on  the  mitral  valve.  The  result 
of  intravenoits  injection  of  the  Diplococcus  rheu- 
maticus. 


FIG.  7o 

The  heart  of  a  monkey.  The  left  ventricle  is  laid 
open  and  the  mitral  valve  exposed.  There  are  vegeta- 
tions on  the  mitral  valve  and  pya?mic  abscesses  in  the 
myocardium.  The  result  of  intravenous  injection 
of  the  Staphylococcus  pyogenes  aureus  and  the 
Diplococcus  rheumaticus. 


.■:•:..•:-. 


*-•**'      -.;-.•:'  •;-;<■£' 


FIG. 


Section  through  the  myocardium  of  the  heart  (Fig-. 
(Zeiss,  obj.  TV,  oc.  4.) 


69)  shoTring  fatty  degeneration. 


PYOGENES  AUREUS  TO  RHEUMATIC  FEVER    219 

Wassermann.  It  was  obtained  from  a  case  of  fatal  chorea 
and  rheumatic  fever.  This  micro-organism  produced  in 
different  animals  these  differing  results  :  a  transitory  arthritis  ; 
an  arthritis  with  endocarditis  and  infarcts  in  the  lungs,  kidneys 
and  spleen  ;  and  an  acute  illness  fatal  on  the  third  day,  with 
early  endocarditis  and  arthritis. 

Thus  it  must  be  admitted  that  rheumatic  fever  may  cause 
something  more  than  fleeting  inflammation. 

But,  although  we  have  not  demonstrated  the  Staphylococcus 
aureus  as  a  cause  of  rheumatic  fever,  it  must  needs  be  that  our 
investigations  have  not  been  very  numerous.  Taking  into 
account  the  earlier  work  of  Dr.  Paine  and  Dr.  Poynton,  some 
twenty-five  fatal  cases  of  rheumatic  fever  form  the  basis  of  this 
investigation,  and  compared  with  the  frequency  of  the  occur- 
rence of  the  disease,  these  only  represent  a  small  total.  It  may 
be  objected,  then,  that  this  evidence  is  insufficient,  and  for  this 
reason  we  have  further  studied  the  experimental  results  pro- 
duced in  rabbits  by  the  Staphylococcus  aureus  in  pure  culture. 
Before  dwelling  upon  these  experimental  results  we  should 
like  to  protest  against  that  attitude  of  mind  which  expects  that 
a  micro-organism  should  produce  infallibly  a  constant  result  in 
animals.  Pathogenic  organisms  are  not  always  pathogenic  to 
man,  nor  do  they  always  when  they  are  pathogenic  produce  a 
regulation  disease  ;  the  same  is  equally  true  of  animals.  Our 
excuse  for  this  obvious  remark  must  be  this,  that  from  time  to 
time  the  objection  is  brought  forward  that  the  results  of  inocula- 
tion of  animals,  especially  rabbits,  are  quite  unreliable.  That 
has  not  been  our  experience,  and  we  are  convinced  that,  if  the 
disease  in  the  animal  is  studied  as  the  disease  in  man,  a  definite 
conclusion  can  be  arrived  at,  so  far  as  rheumatic  fever  is 
concerned. 

The  experimental  results  from  the  inoculation  of  the  Staphy- 
lococcus aureus  are  well  known,  but  we  have  repeated  them 
again,  and  one  of  us  had  already  repeated  them  with  Dr.  Paine 3 
with  th,e  special  object  in  view  of  producing  conditions  similar 
to  those  which  result  from  inoculation  of  the  diplococcus  of 
rheumatic  fever.  Since  one  of  us  (.W.  V.  S.)  has  recently  re- 
corded4 the  results  of  inoculation  of  the  diplococcus  into 
monkeys  we  have  been  able  to  amplify  this  part  of  the  investi- 
gation in  a  direction  which  is  of  considerable  interest,  and  which 
has  strengthened  our  belief  in  the  entity  of  rheumatic  fever. 


220         RELATION  OF  THE  STAPHYLOCOCCUS 

The  result  of  intravenous  inoculation  of  the  Staphylococcus 
aureus  into  rabbits  is  in  the  vast  majority  of  cases  to  produce  : 
(i)  septicaemia  and  rapid  death  without  local  lesions  but  with 
much  haemolysis  ;  or  (2)  pyaemia  with  abscess  formation  in  the 
kidneys,  spleen,  heart-wall  or  elsewhere  ;  or  (3)  no  result  at  all. 

If,  instead  of  intravenous  inoculation,  an  injection  is  made 
locally  into  such  a  joint  as  a  knee-joint,  the  illness  is  more 
gradual,  but  abscesses  form  in  the  various  organs,  and  in  rare 
cases  endocarditis  of  the  ulcerative  type  may  occur. 

The  micro-organism  can  be  easily  recovered  from  the  blood 
in  which  it  produces  great  haemolysis,  and,  speaking  generally, 
the  tendency  of  the  disease  is  to  produce  either  a  fatal  result 
or  no  effect. 

The  usual  results  of  the  inoculation  of  rabbits  intravenously 
with  the  diplococcus  are  as  follows  :  After  an  incubation 
period  of  about  one  to  three  days,  during  which  time  the  animal 
may  show  a  rise  of  temperature,  the  heart  becomes  excited, 
arthritis  develops  in  one  or  more  joints,  especially  those  of 
the  knee  and  carpus,  mitral  endocarditis,  pleuro-pneumonia 
and  pericarditis  may  follow',  and  the  animal  as  a  rule 
dies  from  the  cardiac  inflammation.  Nodules,  choreiform 
movements,  haemorrhages,  iritis  and  nephritis  have  been 
noticed  in  exceptional  cases.  We  have  never  met  with  an 
abscess  in  the  kidneys,  spleen,  liver  or  heart-wall,  but  have 
observed  white  infarcts  in  the  kidneys.  The  duration  of  the 
illness  varies,  but  if  it  is  fatal,  death  usually  occurs  between 
seven  and  twenty-one  days.  Recovery  is  not  uncommon, 
and  this  after  very  definite  symptoms  of  the  infection  have 
developed  ;  or  again,  chronic  articular  inflammation  with 
osteo-arthritic  changes  may  result  and  persist  for  months,  the 
animal  having  otherwise  recovered.  The  endocarditis  may 
affect  the  mitral,  aortic  or  tricuspid  valve,  but  with  by  far  the 
greatest  frequency  the  mitral  is  the  one  attacked. 

It  may  be  a  simple  or  a  vegetative  endocarditis,  and  every 
grade  between  these  can  be  demonstrated.  Septicaemia  we 
have  not  seen,  even  with  large  injections,  but  a  negative  result 
is  not  uncommon  after  small  injections. 

The  diplococcus  can  be  recovered  in  pure  growth  from  the 
advanced  exudations,  but  not  with  certainty  from  the  blood. 
When  a  monkey  has  been  injected  intravenously  the  following 
symptoms  have  been  observed  by  one  of  us  (W.  V.  S.),  and 


„© 

**\- 


FIG.   72 

Blood  film  from  a  monkey  dead  from  the  intravenous  injection  of 
the  Diplococcus  rlieumaticus  and  the  Staphylococcus  pyogenes  aureus. 
The  film  shows  the  diplococcus  in  chain  form,  the  staphylococcus  in 
clusters.  Both  micro-organisms  were  isolated  from  the  tissue. 
(Zeiss,  obj.  TV,  oc.  12.) 


FIG.  73 

Experimental  arthritis  (mixed  infection ).  A  film  from  the  exudation 
into  the  knee-joint  of  a  monkey  dead  from  the  simultaneous  intra- 
venous injection  of  the  Diplococcus  rlieumaticus  and  the  Staphy- 
lococcus pyogenes  aureus.  Both  micro-organisms  are  present  in  the 
film,  the  diplococcus  in  chains,  the  staphylococcus  in  groups. 
(Zeiss,  obj.  TV,  oc.  12). 


PYOGENES  AUREUS  TO  RHEUMATIC  FEVER    221 

were  published  in  the  Journal  of  Pathology  and  Bacteriology  for 
December  1903. 

1.  In  one  case  a  transient  arthritis  supervening  about  twelve 
hours  after  infection. 

2.  In  another,  a  multiple  arthritis  followed  by  pericarditis, 
endocarditis,  and  myocarditis.  The  exudations  were  sero- 
fibrinous ;  there  were  also  hemorrhagic  infarcts  found  in  the 
kidneys  ;  there  were  some  patches  of  broncho-pneumonia  and 
enlargement  of  the  spleen.     Death  occurred  on  the  fourth  day. 

3.  In  a  third  case,  multiple  arthritis  of  much  severity  followed 
infection,  and  later  a  mitral  systolic  murmur  developed,  but  the 
animal  made  a  good  recovery,  and  is  still  alive  four  months 
later. 

The  diplococcus  can  be  recovered  in  pure  growth  from  the 
exudations. 

We  are  of  opinion  that  anyone  who  makes  an  experimental 
study  of  these  two  micro-organisms,  or  who,  failing  this,  trusts  to 
the  evidence  of  repeated  observation  by  others,  must  conclude 
that  the  weight  of  experimental  investigation,  even  when 
divorced  from  clinical  observation,  is  opposed  to  the  acceptance 
of  the  Staphylococcus  aureus  as  a  cause  of  rheumatic  fever. 

In  these  investigations  of  ours  care  was  taken  to  put  these 
two  bacteria  under  the  same  conditions  out  of  the  body,  and  to 
use  them  in  varying  degrees  of  virulence.  We  are  thus  con- 
vinced that  there  is  a  wide  difference  in  the  nature  of  the  two 
infections. 

But  there  is  another  problem  connected  with  the  Staphylo- 
coccus aureus  :  Can  this  micro-organism  produce  a  disease 
indistinguishable  from  rheumatic  fever  if  that  infection  is  a 
mixed  one  ?  The  clinical  study  of  these  mixed  infections  is 
one  of  the  greatest  difficulty,  and  at  the  present  time  it  is  almost 
impossible  to  judge  of  the  relative  parts  taken  in  a  disease 
by  two  infective  agents.  It  is  possible,  nevertheless,  that 
something  may  be  learnt  from  an  experimental  study  of  this 
proble^m,  especially  if  clinical  facts  can  be  steadily  accumulated 
for  comparison  with  such  investigations.  The  two  micro- 
organisms we  are  studying  in  this  paper  give,  as  we  have  shown, 
very  different  experimental  results,  and  so  we  have  tried  the 
effect  of  the  injection  of  mixed  cultures  simultaneously,  and 
the  effect  also  of  the  injection  of  the  Staphylococcus  aureus  after 
previous  infection  with  ' '  ^  diplococcus  of  rheumatic  fever. 


222  RELATION  OF  THE  STAPHYLOCOCCUS 

The  animals  we  have  used  have  been  rabbits  and  monkeys. 
To  make  a  brief  summary  of  our  results  :  we  found  in  the  first 
place  when  the  injections  were  simultaneous  that  the  presence 
of  the  Staphylococcus  aureus  impressed  itself  by  rendering  the 
disease  unlike  rheumatic  fever  and  like  pyaemia,  and  that  this, 
the  more  virulent  organism,  caused  us  special  difficulty  in 
making  observations,  because  the  death  of  the  animals  was 
often  very  rapid.  If  the  animal  had  already  shown  signs  of 
rheumatic  fever,  then  the  staphylococcus  killed  it  with  the 
evidences  of  septicaemia  and  abscess  formation.  The  effect 
of  simultaneous  injection  with  both  micro-organisms  was  well 
shown  in  the  case  of  a  monkey.  Death  occurred  on  the  fifth 
day.  During  this  time  extensive  arthritis  developed,  with 
a  fibrinous  exudation,  containing  the  diplococcus  in  great 
numbers.  There  was  mitral  endocarditis,  and  in  addition 
there  were  pyaemic  abscesses  in  the  heart -wall  containing  vast 
numbers  of  the  Staphylococcus  aureus.  The  staphylococcus 
and  diplococcus  were  present  in  the  blood.  Both  micro- 
organisms were  isolated  again  after  death,  the  diplococcus  from 
the  arthritic  exudation  and  the  Staphylococcus  aureus  from  the 
blood. 

With  rabbits  also,  it  was  our  experience  that  the  diplococcus 
was  most  easily  found  in  the  joints,  and  the  Staphylococcus 
aureus  in  the  blood,  and  that  the  type  of  the  disease  was 
pyaemic.  Both  micro-organisms  were  again  isolated  from  the 
animal  tissues.  In  the  solid  tissues  it  is  hardly  possible,  we 
believe,  to  differentiate  the  two  micro-organisms  under  the 
microscope,  for,  although  the  diplococcus  is  more  easily 
decolorised  by  Gram's  method,  that  is  a  comparative  test 
difficult  to  apply  in  the  tissues.  In  the  exudations  the  strepto- 
coccal arrangement  of  the  diplococcus  is  helpful,  and  the 
occurrence  of  the  staphylococcus  in  masses  in  the  pyaemic 
abscesses  is  also  characteristic. 

Our  preparations  will  show  that  it  is  possible  to  differentiate 
the  two  micro-organisms  in  the  fluid  tissues  and  by  culture,  but 
so  far  as  a  solid  tissue  is  concerned — for  example,  a  mitral 
valve — we  hesitate  to  state  dogmatically  that  the  micro- 
organism present  is  the  diplococcus  or  staphylococcus,  or 
whether  both  are  present  in  the  lesion. 

We  have  alluded  to  the  rapid  deaths  of  the  animals  from  the 
presence  of  the  Staphylococcus  aureus.     This  we  endeavoured 


FIG.   74 

A  section  through  a  pyreniic  ahscess  in  the  myocardium  of  a  monkey 
dead  from  the  simultaneous  intravenous  injection  of  the  Biplococcus 
rheumaticus  and  the  Staphylococcus  pyogenes  aureus,  showing  great 
numbers  of  the  Staphylococcus  nun  us  in  the  necrotic  tissue,  from 
the  same  animal  as  the  preceding.  Death  resulted  on  the  fourth, day 
from  pya?mia.  Both  the  micro-organisms  were  recovered  from  the 
tissues.     (Zeiss,  obj.  TV,  oc.  4.) 


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FIG.  75 


Experimental  endocarditis  (mixed  infection).  Section  through  a 
minute  vegetation  on  the  mitral  valve  of  the  heart  of  a  monkey. 
The  vegetation  shows  the  structure  of  the  ordinary  rheumatic  form, 
and  the  arrangement  and  appearance  of  the  micrococci  lead  to  the 
belief  that  this  was  a  rheumatic  lesion.     (Zeiss,  obj.  iV,  oc.  2.) 


PYOGENES  AUREUS  TO  RHEUMATIC  FEVER     223 

to  overcome  by  inoculating  mixed  cultures  directly  into  the 
knee-joints  of  rabbits. 

The  animals  then  survived  a  longer  time,  but  as  before 
developed  pyaemia  with  abscesses  in  the  liver  and  spleen. 
Again  the  diplococcus  was  found  most  easily  in  the  arthritic 
exudations,  the  Staphylococcus  aureus  in  the  blood  and  spleen. 

We  conclude,  then,  that  the  Staphylococcus  aureus,  when 
injected  into  these  animals  in  association  with  the  diplococcus, 
tends  to  alter  the  type  of  the  disease  from  that  of  rheumatic 
fever  to  that  of  pyaemia  and  staphylococcic  septicaemia. 

This  conclusion,  so  far  as  one  can  apply  it  to  clinical  medicine, 
upholds  our  opinion  that  rheumatic  fever  is  not  a  result  of  the 
staphylococcic  infection,  and  should  a  staphylococcic  infection 
supervene  upon  the  rheumatic  the  tendencies  would  be  twofold  : 

1.  To  accelerate  death. 

2.  To  produce  a  condition  of  pyaemia  rather  than  malignant 

endocarditis. 

Our  clinical  opportunities  of  studying  mixed  infections  have 
been  few,  but  in  1901  Dr.  Paine  and  Dr.  Poynton  had  the 
opportunity  of  studying  such  a  case  in  a  child. 

A  boy  aged  8§  years  was  admitted  on  February  15,  1901,  to 
the  Hospital  for  Sick  Children,  Great  Ormond  Street,  suffering 
from  cellulitis  of  the  right  leg,  the  result  of  a  sore  on  the  heel. 
The  limb  was  incised,  but  no  pus  escaped.  Three  days  after- 
wards he  complained  of  pain  in  the  right  hip,  and  the  next  day 
of  pain  in  the  left  hip.  Upon  the  24th  loud  pericardial  friction 
was  heard,  and  upon  March  1,  there  was  pain  in  the  left 
shoulder. 

Several  who  saw  this  child,  though  well  acquainted  with  the 
fact  of  the  cellulitis,  suspected  that  this  illness  might  be  rheu- 
matic fever  because  of  the  low  range  of  temperature,  the 
absence  of  shivering  and  rigors,  the  slight  distress,  and  the  loud 
pericardial  friction.  The  child  died  on  March  4,  and  at 
the  post-mortem  there  were  found  purulent  pericarditis 
and  arthritis,  with  abscesses  in  the  kidneys  and  lungs.  Dr. 
Paine  took  cultures  from  the  pericardium  and  left  hip-joint. 
In  each  case  the  result  was  a  mixed  one  of  the  Staphylo- 
coccus aureus  and  a  minute  diplococcus.  This  case  exemplifies 
the  point  we  emphasised  earlier — the  importance  of  a  com- 
plete investigation.  Many  of  the  clinical  features  of  the  case 
resembled  those   of  rheumatic  fever  ;   the  necropsy  showed 


224  THE  STAPHYLOCOCCUS  AND  RHEUMATIC  FEVER 

conclusively  that  it  was  not  rheumatic  fever.  The  bacteriologist 
demonstrated  it  to  be  a  mixed  infection,  and  the  Staphylococcus 
aureus  as  a  cause  of  the  pyaemic  condition. 

We  put  forward,  then,  these  two  statements  based  on  this 
investigation  : 

(i)  The  Staphylococcus  aureus  is  not  a  cause  of  rheumatic 

fever  either  in  simple  or  mixed  infection. 
(2)  Rheumatic  fever  is  not  an  attenuated  pyaemia,  so  far  as 
the  Staphylococcus  aureus  is  concerned. 

REFERENCES 

1  "  Le  Rheumatisme  Articulaire  aigu." 

2  "  On  the  Pathology  of  Acute  Rheumatism  and  Allied  Conditions," 
Brit.  Med.  Journ.,  September  19,  1903. 

3  "  A  Contribution  to  the  Study  of  Malignant  Endocarditis,"  Med.- 
Chir.   Trans.,   1902. 

*  Journal  of  Pathology  and  Bacteriology,  December  1903. 


PART  II 

SUB-GROUP  D 

THE  GREATER  PART  OF  THESE  PAPERS  IS  DEVOTED 
TO  THE  ELUCIDATION  OF  SOME  OF  THE  IMPORTANT 
NERVOUS  MANIFESTATIONS  OF  ACUTE  RHEUMA- 
TISM. WE  WERE  FORTUNATE  ENOUGH  TO  OBTAIN 
THE  COLLABORATION  OF  DR.  GORDON  HOLMES 
IN  ONE  OF  THEM  DEALING  WITH  THE  MINUTE 
PATHOLOGY  OF  CHOREA 

IN  THIS  SUB-GROUP  SOME  SPACE  HAS  BEEN  GIVEN 
TO  ANSWERING  THE  CRITICISMS  OF  OUR  PREVIOUS 
RESULTS,  WHICH  HAD  STEADILY  ACCUMULATED. 
IT  WOULD  HAVE  BEEN  AN  INJUSTICE  TO  OUR 
CRITICS  AND  TO  OURSELVES  IF  WE  HAD  NOT 
RETAINED  THIS  PART  OF  THE  WORK,  WHICH 
HELPS,  WE  FELT,  TO  SHOW  THAT  WE  DID  NOT 
OVERLOOK  SUCH  CRITICISMS  BUT  ATTEMPTED 
TO  MEET  THEM  BY  FURTHER  INQUIRY.  THIS 
DUTY  WAS  THE  MORE  IMPERATIVE  BECAUSE  THE 
SUBJECT  THAT  WE  DEAL  WITH  IS  ONE  OF  MUCH 
INTEREST  AND  GENERAL  MEDICAL  IMPORTANCE 

XVIII.  SOME  INVESTIGATIONS  UPON  THE  NERVOUS  MANI- 
FESTATIONS OF  ACUTE  RHEUMATISM 

XIX.  A  CONTRIBUTION  TO  THE  PATHOLOGY  OF  CHOREA 
BY  DR.  F.  J.  POYNTON  AND  DR.  GORDON  HOLMES 

XX.  SOME    FURTHER    INVESTIGATIONS    AND  OBSERVA- 
TIONS UPON  THE  PATHOLOGY  OF  RHEUMATIC  FEVER 


225  15 


PAPER  NO.  XVIII 

SOME  INVESTIGATIONS   ON  THE  NERVOUS 
MANIFESTATIONS  OF  ACUTE  RHEUMATISM  ' 

(Reprinted  from  the  Lancet,  December  1905.) 

The  first  part  of  this  paper  is  mainly  retrospective,  and  concerned 
with  answering  criticisms  raised  by  our  previous  communications. 
The  second  part  brings  forward  some  new  facts  bearing  upon  the 
pathology  of  rheumatic  chorea.  The  third  deals  with  a  very  remarkable 
case  of  cerebrospinal  meningitis  following  upon  a  mild  attack  of 
rheumatic  fever.  This  paper  was  read  at  a. meeting  of  the  Neurological 
Society  of  the  United  Kingdom,  with  the  intention  of  inviting  discussion 
upon  the  casg  oj  cerebrospinal  meningitis,  but  unfortunately  there  had 
been  a  desire  expressed  to  throw  open  the  entire  question  of  the  cetiology 
of  acute  rheumatism,  with  the  result  that  no  further  light  was  thrown 
upon  this  particular  case.  We  have  published  it  again  here,  for  the 
bacteriological  investigations  that  were  undertaken  to  differentiate  the 
dipiococcus  from  the  pneumococcus  were  prolonged  and  minute,  and 
resulted  in  the  conviction  in  our  minds  that  the  meningitis  was  not  due 
to  a  secondary  pneumococcic  invasion. 

Dr.  Beattie  in  1904  had  published  the  first  of  his  numerous  investi- 
gations upon  the  cause  of  acute  rheumatism,  which  have  supported 
our  investigations  and  added  new  facts  to  the  subject. 

We  commence  this  paper  by  putting  forward  our  present 
attitude  towards  the  aetiology  of  acute  rheumatism  and 
answering  some  of  the  objections  that  have  been  raised 
against  our  interpretation,  for  we  feel  that  if  we  do  not 
take  this  precaution  the  particular  points  bearing  upon  the 
nervous 'system  which  are  the  subject  of  this  paper  will  seem 
to  rest  upon  an  insecure  basis. 

Part  I. — The  /Etiology  of  Acute  Rheumatism 

Five  years  ago  in  a  paper  published  in  the  Lancet 2  we 
claimed  that  we  had  proved  that  a  dipiococcus  was  a  cause  of 

227 


228  INVESTIGATIONS  OX  THE  NERVOUS 

rheumatic  fever — a  cause  that  had  been  hazarded  by  others 
in  England,  Germany,  and  France  before  the  publication  of 
our  article.3  Two  years  later  before  the  Royal  Medical  and 
Chirurgical  Society  4  we  showed  that  rheumatic  fever  might 
be  a  cause  of  malignant  as  well  as  so-called  simple  endo- 
carditis. Since  then  and  up  to  the  present  time  we  have 
been  gradually  filling  in  the  gaps  in  our  knowledge  and 
strengthening  the  weaker  links  in  the  chain  of  proof.  Our 
position  now  has  not  altered  :  we  still  firmly  maintain  that 
this  diplococcus  is  a  cause  of  rheumatic  fever  ;  and  further, 
we  believe  it  to  be  the  only  bacterial  cause  ;  we  also  maintain 
that  rheumatic  fever  is  a  cause  of  malignant  endocarditis. 

These  views  clearly  imply  that  we  hold  that  there  is  a 
definite  disease — rheumatic  fever.  We  do  firmly  believe  this 
and  hold  that  it  is  as  definite  a  disease  as  tuberculosis.  There 
are,  admittedly,  cases  of  rheumatic  fever  that  are  most  difficult 
to  differentiate,  but  they  are  no  more  numerous  or  more 
puzzling  than  are  difficult  cases  of  tuberculosis  or  typhoid 
fever.  These  views  imply,  too,  that  we  have  satisfied  Koch's 
postulates.  We  believe  that  we  have  done  so,  and  at  various 
societies  in  London  and  at  the  International  Congress  in 
Madrid  5  we  have  demonstrated  the  micro-organism,  its  pure 
cultures,  and  its  presence  in  the  human  and  animal  tissue 
damaged  by  rheumatism.  We  have  isolated  it  now  from 
32  cases  of  undoubted  rheumatic  fever  and  the  disease  can  be 
produced  not  only  in  rabbits  but,  as  Dr.  Vernon  Shaw  6  has 
shown  with  one  of  our  cultures,  in  monkeys  also. 

On  the  other  hand,  we  have  never  maintained  that  this 
diplococcus  was  specific  except  in  so  far  that  it  is,  in  our 
opinion,  the  only  bacterial  cause  of  a  specific  disease.  We  set 
ourselves  to  prove  that  it  was  a  cause  of  a  specific  disease  and 
left  for  future  investigation  the  next  step — the  demonstration 
of  a  distinctive  laboratory  test  for  the  micro-organism.  A  very 
different  undertaking  this  one,  yet  only  too  often  confused  with 
the  first  ;  indeed,  we  venture  to  put  this  question  prominently 
forward  :  Does  a  demonstration  of  a  bacterial  cause  of  a 
disease  demand  the  demonstration  of  a  specific  test  for  the 
bacterium  ? 

We  named  the  micro-organism  the  "  diplococcus  rheu- 
maticus  " — a  name  which  has  aroused  a  little  criticism.  Yet 
it  is  a  reasonable  and  accurate  name  and  for  these  reasons,  in 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    229 

our  opinion,  the  best  name.  It  is  reasonable  because  the 
bacterium  is  a  cause  of  rheumatic  fever,  and  it  is  accurate 
because  a  diplococcus  expresses  the  usual  appearance  of  the 
micro-organism.  Some  hold  that  the  name  is  badly  chosen, 
because  it  implies  that  the  micro-organism  is  specific,  but 
clearly  it  in  no  way  interferes  with  the  appearance  on  the  scene 
of  a  spirochaete  or  trypanosoma  rheumaticus.  Others  hold 
that  it  is  badly  chosen  because  the  adjective  "  rheumaticus  " 
implies  that  rheumatism  is  a  definite  disease  ;  our  answer  to 
this  is  that  acute  rheumatism  or  rheumatic  fever  is  a  definite 
disease,  and  that  if  the  term  rheumatism  has  any  accurate 
meaning  it  should  have  one  corresponding  to  that  which  the 
term  tuberculosis  bears  in  relation  to  acute  tuberculosis  or 
tuberculous  fever. 

There  are  some  who  believe  that  rheumatic  fever  is  not  the 
result  of  an  infection.  They  ought,  we  think,  to  demonstrate 
some  non-infective  cause  and  then  to  explain  the  coincidence 
that  a  bacterium,  which  has  been  found  in  the  arthritis,  endo- 
carditis, pericarditis,  subcutaneous  nodules,  pleurisy,  pneu- 
monia, peritonitis,  and  nephritis  of  rheumatic  fever,  is  able  to 
produce  similar  lesions  in  animals.  Should  they  look  upon  all 
these  lesions  as  complications  they  should  define  rheumatic 
fever  when  these  lesions  are  put  aside  as  epi -phenomena.  Many 
more  believe  that  rheumatic  fever  is  a  result  of  many  different 
infections.  If  one  other  micro-organism  even  can  be  said  to 
have  fulfilled  Koch's  postulates  with  reasonable  constancy 
some  one  should  bring  forward  the  evidence  in  its  favour  by  a 
clear  and  decisive  demonstration.  Lastly,  there  are  others  who 
believe  rheumatic  fever  is  a  definite  disease  and  that  it  is 
infective,  but  that  the  infection  has  not  yet  been  demonstrated. 
This  view  naturally  implies  that  the  evidence  in  favour  of  this 
diplococcus  is  not  convincing. 

It  is  not  convincing  in  the  opinion  of  some  because  the 
diplococcus  is  not  constantly  present  ;  indeed,  they  would  go 
further,  and  say  it  is  generally  conspicuous  by  its  absence, 
or  if  it  is  present  that  it  is  only  found  after  death.  These 
objections  we  can  only  meet  by  a  counter-statement,  to  the 
effect  that  it  is  found  ante-mortem  and  post-mortem  and  that 
in  suitably  chosen  cases  it  is  found  with  remarkable  constancy. 
We  have  ourselves  found  it  in  32  cases  and  many  others  have 
isolated  a  diplococcus  in  acute  rheumatism,  notably,  Ainley 


230  INVESTIGATIONS  ON  THE  NERVOUS 

Walker  7  and  Beatson,  Beattie  8  and  Vernon  Shaw  in  this 
country,  von  Leyden,9  Triboulet,  and  Coyon,10  Wassermann,11 
Predtetschensky,12  Meyer,13  Singer,14  Allaria,15  Jarvis,16  Cole,17 
Longcope,18  and  Herry.1? 

Never  easy  to  find,  it  is  very  difficult  to  discover  if  searched 
for,  as  it  was  searched  for  by  Philipp,20  in  unlikely  places  such 
as  the  blood  and  arthritic  exudations.  The  micro-organism 
multiplies  and  flourishes  in  the  local  lesions  and  the  blood 
stream  is  only  a  channel  of  conduction  ;  further,  rheumatic 
septicaemia,  as  clinical  experience  teaches  us,  is  rare,  although 
two  such  instances  have  occurred  in  our  experience.  Apart 
from  these  very  exceptional  instances  we  have  several  times 
isolated  it  from  the  blood  ante-mortem  but  the  blood  stream  is 
certainly  not  a  favourable  site  from  which  to  isolate  the  micro- 
organisms in  an  ordinary  case  of  acute  rheumatism.  Another 
unlikely  place  is  the  arthritic  exudation,  because  the  micrococci 
are  deposited  in  the  areolar  tissue  below  the  free  margin  of  the 
synovial  membrane  and  the  cells  lining  the  synovial  cavity 
are  phagocytic.  Not  only  this,  numerous  leucocytes  also 
escape  into  the  synovial  tissues  and  aid  in  the  destruction  of 
the  micrococci.  Then,  again,  the  amount  of  exudation  is 
comparatively  small  and  the  exudate  itself  containing  leuco- 
cytes and  endothelial  cells  will  destroy  the  bacteria.  If  these 
reasons  are  not  sufficient  we  would  add  that  rheumatic  arthritis 
is  the  most  easily  overcome  of  all  the  lesions  and  that  in 
animals  which  have  been  experimentally  inoculated  with  the 
diplococcus  and  in  which  as  a  result  arthritis  has  developed 
wre  may  fail  to  isolate  the  micrococcus  from  the  fluid  when  this 
arthritis  is  in  the  early  stage.  This  has  happened  to  us 
repeatedly.  It  is  of  considerable  interest  also,  as  bearing  upon 
this  point,  that  antitoxic  sera  free  from  bacteria  may  some- 
times produce  effusion  into  joints  and  this  makes  it  very 
probable  that  the  poisons  formed  by  the  diplococci  in  the 
synovial  tissue  can  of  themselves  produce  an  effusion  into  the 
synovial  cavity.  Dr.  Beattie  has  kindly  sent  us  a  note  from  a 
further  research  which  he  has  not  yet  published  of  a  case  in 
which  he  found  in  a  man  dead  from  rheumatic  fever  that  the 
exudation  was  sterile  but  the  congested  areas  of  the  synovial 
membrane,  removed  with  all  precautions,  gave  a  pure  growth 
of  the  diplococcus.  This  is  a  most -striking  independent  proof 
of  our  assertion. 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    231 

Although,  then,  the  arthritic  exudation  is  not  a  fluid  in  which 
it  is  easy  to  find  the  diplococcus,  yet  it  can  be  found,  and  has 
been  found,  by  ourselves  and  others  both  ante-mortem  and 
post-mortem.  On  the  other  hand,  it  can  only  be  a  fair  question, 
if  we  maintain  that  the  micro-organism  can  be  found  in  suitable 
cases  with  remarkable  constancy,  to  ask  what  are  the  suitable 
cases  ?  They  are  acute  and  severe  ones,  in  which  the  lining 
membranes  of  the  serous  cavities  are  greatly  damaged  or  in 
which  the  type  is  malignant.  Sero-fibrinous  pericarditis  and 
malignant  cases  of  rheumatic  endocarditis  are  excellent 
examples.  We  have  only  failed  once  in  recent  cases  of 
fatal  pericarditis  when  adhesions  have  not  been  extensive 
and  in  that  case  we  had  to  deal  with  a  hemorrhagic 
exudation. 

A  good  deal  of  criticism  has  been  devoted  to  the  nature  of 
this  micro-organism  ;  this  criticism  is  of  secondary  importance. 
Whether  or  not  the  diplococcus  is  a  cause  of  rheumatic  fever 
is  clearly  of  first  importance,  but  whether  or  not  it  is  an  altered 
streptococcus  pyogenes  is  of  secondary  importance  because  no 
one  can  define  the  streptococcus  pyogenes.  This  line  of 
criticism,  however,  needs  a  few  words  of  comment.  Take,  for 
example,  an  admirable  and  recent  investigation  by  Rufus  Cole. 
Rufus  Cole,  having  isolated  a  diplococcus  from  a  case  of 
rheumatic  fever,  proceeded  to  work  as  others,  including  our- 
selves, had  done,  with  various  streptococci  isolated  from 
conditions  which  were  certainly  not  rheumatic,  and  thus 
concludes  :  "  Arthritis  and  endocarditis  may  be  produced  by 
the  intravenous  inoculation  of  rabbits  with  streptococci  from 
various  sources,  and  the  results  are  quite  similar  to  those 
described  as  resulting  from  the  inoculation  of  the  so-called 
micrococcus  or  diplococcus  rheumaticus."  Can  anyone,  we 
ask,  say  that  lesions  are  quite  similar  until  they  can  explain  the 
details  of  the  chemical  processes  which  have  produced  them  ? 
Could  we  venture  to  dogmatise  upon  the  exciting  cause  of 
an  early  arthritis  or  endocarditis  in  man  by  looking  at  the 
lesion  'with  the  naked  eye  or  even  under  the  microscope  ? 
Could  we,  for  example,  say  this  is  gonococcic,  rheumatic, 
penumococcic  or  influenzal  or  staphylococcic  ? 

Not,  however,  content  with  this  conclusion,  investigators 
working  on  these  lines  go  further  and  say  that  the  rabbit  is 
quite  useless  as  a   test,  for  you   can  produce  arthritis  and 


232  INVESTIGATIONS  ON  THE  NERVOUS 

endocarditis  in  it  with  various  micrococci  and  the  occurrence 
proves  nothing.  They  forget  monkeys  as  well  as  rabbits  are 
susceptible  to  the  rheumatic  infection  and  the  fact  that  the  first 
two  of  Koch's  postulates  must  be  satisfied — you  must  find 
the  organism  in  the  human  disease  you  are  studying  and 
isolate  it  from  the  lesions.  No  one  has  yet  claimed  that  at 
present  these  two  postulates  can  be  ignored  in  studying  the 
cause  of  rheumatism  and  it  is  obviously  impossible  to  do  so 
until  the  specific  test  for  the  bacterium  has  been  discovered. 
Then  is  it  so  remarkable  that  the  rabbit  is  susceptible  to  many 
causes  of  arthritis  and  endocarditis.  Is  rheumatism  the  only 
cause  of  these  conditions  in  man  ?  Have  not  we  heard,  for 
instance,  of  gonorrhceal,  staphylococcic,  meningococcic,  pneu- 
mococcic,  scarlatinal,  tuberculous  and  influenzal  endocarditis 
and  arthritis,  yet  is  it  quite  useless  to  attach  any  importance 
to  endocarditis  and  arthritis  as  evidences  of  rheumatism  in 
man  ? 

Another  statement  we  have  frequently  heard  is  to  the  effect 
that  this  diplococcus  is  only  an  attenuated  streptococcus 
pyogenes.  Surely  this  is  a  confession  of  lack  of  clinical 
knowledge.  Could  anyone  who  has  thoroughly  studied  acute 
rheumatism  believe  it  to  be  the  result  of  any  attenuated 
process  ?  It  is  remarkable,  too,  how  pyaemia  has  disappeared 
since  the  antiseptic  treatment  of  wounds  has  been  introduced 
and  yet  rheumatic  fever  cannot  be  said  to  be  any  less  common. 
What  is  to  be  said  of  the  scientific  value  of  that  widespread 
doctrine  that  salicylate  of  sodium  is  a  test  of  rheumatism  ? 
We  think  that  it  assumes  too  much  that  is  at  present  unknown. 

The  great  difficulty  at  the  present  time  is,  then,  to  find  a 
specific  test  or  specific  tests  for  this  diplococcus  by  which  we 
can  recognise  it  from  other  streptococci  and  it  is  a  difficulty 
that  will  probably  test  the  most  skilful  bacteriologists  and 
chemists.  Gram's  stain  and  morphological  and  cultural 
characteristics  do  not  carry  the  weight  they  did  ;  bacteriology 
is  getting  older  and  is  more  cautious  with  its  use  of  the  word 
'•  specific."  We,  however,  maintain  that  a  failure  to  find  a 
specific  laboratory  test  in  no  way  alters  the  conclusions  that 
the  bacterium  is  a  cause  of  acute  rheumatism  or  that  acute 
rheumatism  is  a  specific  disease.  The  best  test  of  a  bacterium, 
though  not  the  most  practically  useful  one,  is  the  satisfaction 
of    Koch's   postulates.      We   should   not  like  it,  however,  to 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    233 

be  thought  that  we  have  neglected  to  attempt  a  differen- 
tiation ourselves,  or  have  not  appreciated  the  efforts  of  other 
investigators  in  this  direction. 

The  diplococcus  has,  in  our  opinion,  these  peculiarities  : 

1.  Morphologically,  it  is  minute  and  smaller  than  the 
streptococcus  pyogenes.  The  diplococcal  arrangement  in  early 
cultures  is  more  constant  and  it  does  not  retain  Gram's  stain 
so  well.  Lastly,  it  resists  drying  in  the  most  remarkable  way 
for  six  months  or  even  longer,  which  we  believe  is  very  different 
from  the  character  of  the  streptococcus  lanceolatus. 

2.  Physiologically,  it  causes  an  early  production  of  acid  and 
a  greater  production  of  acid  than  the  streptococcus  pyogenes. 
On  this  account  it  produces  a  firm  clot  in  milk.  The  diplo- 
coccus will  grow  in  a  filtered  culture  of  the  streptococcus 
pyogenes.  Ainley  Walker  and  Ryffel 21  in  a  most  interesting 
research  have  demonstrated  that  a  considerable  amount  of 
formic  acid  is  produced  by,  and  in,  these  bacteria.  Allusion, 
too,  must  be  made  to  a  recent  paper  by  Gordon  in  the  Lancet 22 
upon  a  ready  method  of  differentiating  streptococci  by  their 
ability  to  decompose  various  chemical  compounds  belonging  to 
the  carbohydrate,  glucoside,  and  polyatomic  alcohol  series,  in 
each  case  with  an  acid  reaction.  No  direct  reference  is  made 
to  the  streptococcus  of  rheumatism,  but  the  general  conclusion 
of  this  investigator  is  interesting.  He  writes  :  "  The  chief 
object  of  my  paper  is  to  show  that  the  individuality  of  strepto- 
cocci is  real,  not  apparent." 

3.  Experimentally,  rabbits  are  more  resistant,  and  arthritis 
and  endocarditis  are  much  more  constant.  It  is  also  difficult 
to  raise  the  virulence.  When  it  produces  rapid  death  in  a 
rabbit  we  have  not  observed  that  remarkable  softening  of  the 
tissues  and  staining  of  the  blood-vessels  seen  in  severe  strepto- 
coccus pyogenes  infections.  And  we  have  never  seen  abscesses 
in  the  kidneys,  heart  wall,  spleen,  or  liver, 

These  may  be  small  points  and  are  certainly  far  from 
specific  tests,  but  taken  together  they  have,  we  believe,  some 
value.  It  certainly  seems  to  us  that  the  most  satisfactory 
working  theory  at  present  is  to  look  upon  rheumatism  and  its 
allies  as  one  looks  upon  a  group  of  chemical  elements,  such  as 
chlorine,  bromine,  iodine,  and  fluorine— that  is  to  say,  there  is 
much  in  common  among  them,  yet  each  constituent  of  the 
group  is  in  itself  peculiar.     To  summarise,  we  hold  that  there 


234  INVESTIGATIONS  ON  THE  NERVOUS 

is  a  great  infective  process,  the  rheumatic,  to  be  placed  among 
that  series  of  infective  processes  where  the  staphylococcus, 
streptococcus,  pneumococcus,  and  gonococcus  are  to  be  found, 
and  that  the  infective  agent  is  a  diplococcus  with,  in  all 
probability,  some  peculiar  characters. 


Part  II. — Chorea 

Passing  now  to  the  particular  investigations  which  prompted 
us  to  write  this  paper,  the  first  have  reference  to  chorea.  In 
May  1901,  in  a  paper  in  the  Lancet,  we  elaborated  in  some 
detail  the  view  that  rheumatic  chorea  was  a  result  of  the 
diplococcus  infection.  We  speak  advisedly  of  rheumatic 
chorea,  not  being  prepared  to  maintain  that  all  chorea  is 
rheumatic,  for  it  may  be  that  other  infections,  especially  of 
the.  streptococcal  group,  can  also  sometimes  produce  this 
condition  and  many  also  believe  that  fright  is  an  exciting  cause. 
With  regard  to  this  latter  point,  as  a  result  of  personal  inquiry 
into  the  history  of  250  cases  of  chorea  under  12  years  of  age, 
we  support  Dr.  D.  B.  Lees's  opinion  that  fright,  as  an  exciting 
cause,  is  greatly  overrated,  but  we  believe  that  it  is,  as  many 
authorities  have  long  maintained,  a  predisposing  one  of  im- 
portance. It  hardly  need  be  said  that  we  believe  implicitly  in 
the  teaching  of  those  who  have  held  that  the  great  majority  of 
cases  of  chorea  are  rheumatic,  and  rheumatic  in  the  sense  that 
the  chorea  is  an  actual  manifestation  of  the  disease.  Here, 
again,  we  would  submit  that  the  clinical  evidence  in  favour  of 
this  view  is  overwhelming. 

If  then,  for  the  moment,  the  diplococcus  is  accepted  as  a 
cause  of  rheumatic  fever,  the  first  essential  in  the  explanation 
of  rheumatic  chorea  is  to  bring  forward  evidence  of  its  presence 
in  the  nervous  system  or  general  circulation  when  the  rheu- 
matism is  active  and  has  been  the  cause  of  death.  Such 
evidence  is  slowly  accumulating.  Thus  a  diplococcus  was 
isolated  under  such  conditions  by  Dana  23  in  1894  and  again 
in  1898  by  Apert,24  who  then  distinctly  stated  that  he  thought 
it  was  identical  with  the  diplococcus  discovered  by  Triboulet 
and  Thiroloix  in  aggravated  rheumatic  fever.  In  1889, 
Westphal,  Wassermann,  and  Malkoff  published  their  important 
case  of  a  child,  dead  from  rheumatic  pericarditis  and  chorea, 
from  whose  pericardial  and  cerebro-spinal  fluids  was  isolated  a 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    235 

diplococcus  which  produced  arthritis  in  a  series  of  80  rabbits. 
These  observers  maintained  that  this  diplococcus  was  the  cause 
of  acute  articular  rheumatism.  In  1900  we  recorded  the 
occurrence  of  choreiform  movements  in  a  rabbit  as  a  result  of 
an  intravenous  inoculation  of  the  diplococcus,  and  in  1901  we 
verified  the  occurrence  of  a  diplococcus  in  the  cerebro-spinal 
fluid  of  a  child  who  had  died  from  severe  rheumatism  with 
chorea.  Fritz  Meyer,  in  1901,  with  a  diplococcus  obtained 
from  rheumatic  angina  faucium,  produced  irregular  choreiform 
movements  in  six  rabbits.  In  1903  Beaton  and  Ainley  Walker 
twice  isolated  a  diplococcus  post-mortem  from  the  heart's  blood 
and  once  ante-mortem  from  the  urine  in  rheumatic  chorea,  and 
in  two  of  these  cases  produced  arthritis  and  endocarditis.     In 

1903,  at  the  International  Congress,25  we  also  brought  forward 
a  fatal  case  of  rheumatism  with  chorea,  in  which  we  had 
isolated  the  diplococcus  from  the  pericardial  fluid  and  pro- 
duced not  only  arthritis,  as  had  Wassermann,  but  also  peri- 
carditis and  endocarditis.  In  1904  Beattie  recorded  the  same 
occurrence  with  a  diplococcus  which  he  had  independently 
isolated  from  a  case  of  fatal  rheumatism.  In  his  case  the 
diplococcus  was  isolated  from  the  arthritic  exudation  and  also 
produced  choreiform  movements  in  a  rabbit. 

Now,  again,  in  two  cases  of  rheumatic  fever  dying  with 
symptoms  of  chorea  we  have  isolated  this  diplococcus  from 
the  cerebro-spinal  fluid.  In  one  case  the  virulence  of  the 
cultures  was  not  sufficient  to  produce  any  experimental  effect  ; 
in  the  second  case,  however,  not  only  was  arthritis  produced 
but  also  endocarditis  and  pericarditis — that  is  to  say,  a  micro- 
organism circulating  in  the  cerebro-spinal  fluid  during  an  acute 
attack  of  rheumatism  with  chorea  was  able  to  produce  such 
lesions  as  arthritis,  endocarditis,  and  pericarditis.  This,  we 
think,  brings  us  a  step  nearer  the  elucidation  of  chorea,  and 
owing  to  the  kindness  of  Dr.  Lees  we  are  enabled  to  give  a 
brief  account  of  this  case.  A  boy,  aged  nine  years,  who  had 
suffered  from  acute  rheumatism  at  three  years  of  age,  was 
admitted  to  St.  Mary's  Hospital  under  Dr.  Lees  on  Nov.  22, 

1904,  in  a  second  attack.  Previously  to  his  admission  he 
had  been  ill  for  seven  weeks  with  sore-throat,  multiple  arthritis, 
and  general  chorea,  and  he  only  lived  two  days  in  the  hospital, 
dying  with  general  pericarditis  and  violent  chorea.  The 
necropsy  showed  a  pericardium  bound  down  by  recent  and  old 


236  INVESTIGATIONS  ON  THE  NERVOUS 

adhesions  but  there  was  no  endocarditis.  The  liver  and 
kidneys  were  engorged,  there  was  pleurisy  with  nbrino-plastic 
exudation,  and  the  brain  was  hyperaemic. 

This,  then,  may  be  looked  upon  as  a  case  of  severe  rheumatic 
fever  in  which  chorea  was  a  notable  manifestation  at  the  time 
of  death.  Cultures  were  made  from  the  blood  in  the  heart, 
the  pericardial  and  cerebro-spinal  fluids,  in  milk  bouillon.  One 
tube  of  blood  from  the  heart  was  sterile  and  one  contained  a 
pure  growth  of  the  diplococcus,  the  tube  with  the  cerebro- 
spinal fluid  contained  a  pure  growth,  and  the  pericardial  fluid 
contained  the  same  micro-organism,  together  with  the  staphylo- 
coccus albus,  from  which  it  was  separated  by  plate  culture. 
Two  inoculations  were  made  from  these  cultures  :  (a)  a  small 
dose  was  injected  subcutaneously  into  a  small  rabbit  ;  and 
(b)  a  large  dose  was  injected  intravenously  into  a  large  rabbit. 
The  first  developed  a  small  inflammatory  nodule  at  the  site  of 
inoculation,  which  disappeared  gradually  without  any  con- 
stitutional symptoms.  The  second,  injected  intravenously, 
died  in  24  hours.  Diplococci  were  present  in  the  blood.  All 
the  organs  were  firm  and  not  soft  as  in  the  case  of  a  septicaemia 
from  a  septic  infection.  The  diplococcus  was  isolated  and 
again  cultivated.  Another  series  of  cultures  was  then  made 
from  the  original  strain  and  three  more  inoculations  were  made 
on  November  30.  (1)  A  five  cubic  centimetre  bouillon  culture 
was  injected  intravenously  into  rabbit  No.  3  ;  (2)  the  contents 
of  three  blood  serum  tubes  were  injected  intravenously  into 
rabbit  No.  4  ;  and  (3)  the  contents  of  three  blood  agar  tubes 
into  rabbit  No.  5.  The  last  of  these  three  animals  developed 
arthritis  on  the  third  day  and  died  on  the  fifth  from  general 
pericarditis,  cardiac  dilatation,  and  mitral  endocarditis.  We 
have  been  asked  whether  we  have  also  obtained  the  diplococcus 
from  the  brain  but  the  question  is  impossible  to  answer, 
because  one  cannot  exclude  the  possibility  of  either  pia  mater 
or  cerebro-spinal  fluid  being  included  in  the  fragments. 

There  have  been  a  certain  number  of  observations  pointing 
to  the  presence  of  the  staphylococcus  aureus  as  a  cause  of 
chorea.  We  have  not  ourselves  been  able  to  trace  such  a 
connection  in  rheumatic  chorea  and  in  the  preceding  paper 
by  Poynton  and  Vernon  Shaw 26  some  evidence  was  brought 
forward  to  show  that  this  micrococcus  was  not  a  cause  of 
rheumatism  and  rheumatic  chorea.     Nevertheless  it  is  quite 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    237 

possible  that  the  aureus  infection  may  produce  chorea  if  we 
admit  that  other  infections  allied  to  the  rheumatic  may  be,  in 
exceptional  cases,  exciting  causes. 

We  would  ask  now  for  the  acceptance  of  the  view  that 
rheumatic  chorea  is  a  result  of  the  diplococcus  infection, 
for  then  we  can  pass  on  to  the  next  consideration — the  nature 
of  the  morbid  lesions.  At  the  outset  we  are  confronted  with 
this  difficulty  :  we  know  that  the  lesions  in  rheumatic  fever 
are  of  the  type  of  pyaemic  lesions — that  is,  they  are  local 
infections  of  various  organs — and  we  also  know  that  there  is  a 
variable  amount  of  general  systemic  poisoning  as  evidenced  by 
the  rapid  anaemia.  Applying  this  knowledge  to  the  nervous 
system  we  have  two  possibilities.  Chorea  may  be  a  result  of 
local  lesions  comparable  to  other  local  rheumatic  lesions,  or  it 
may  be  that  the  delicate  nervous  tissues  are  exceptionally 
sensitive  to  the  general  rheumatic  poisoning.  We  incline  to 
the  view  that  chorea  is  a  result  of  numerous  slight  local  lesions, 
and  it  will  be  at  once  apparent  that  we  are  thus  led  to  a  slight 
modification  of  the  original  views  of  that  illustrious  neurologist, 
Dr.  J.  Hughlings  Jackson.  To  a  slight  modification  in  that 
we  do  not  suppose  that  there  is  actual  embolism,  but  rather 
the  occurrence  of  small  focal  lesions  external  to  the  blood 
capillaries  caused  by  the  escape  of  the  diplococci  which  are 
carried  by  the  blood  stream  into  these  positions.  The  local 
changes  around  the  capillaries  might  cause  haemorrhage, 
thrombosis,  perivascular  exudation,  and  in  chronic  cases  peri- 
vascular fibrosis.  The  poisons  that  are  elaborated  would 
probably  cause  fatty  and  other  destructive  changes  in  the 
nervous  tissues  themselves.  We  should  expect  the  pia  mater 
to  be  definitely  affected  in  chorea  because  of  its  analogy  to  the 
other  serous  membranes  and  because  there  are  an  enormous 
number  of  minute  blood-vessels  in  this  membrane. 

If,  on  the  other  hand,  the  general  systemic  poisoning  is 
responsible  for  chorea  one  almost  despairs  of  getting  any 
nearer  the  solution  of  this  problem  until  the  chemistry  of 
rheumatism  is  elucidated,  for  these  general  systemic  poisonings 
are  beyond  the  reach  of  morbid  anatomy.  Working  along 
these  lines  we  have  attempted  by  intravenous  injections  of 
formic  acid  in  rabbits  to  produce  choreiform  movements,  but 
failed  to  obtain  any  such  result.  Reichart 27  has  recently 
published  accounts  of  a  careful  investigation  of  two  brains  in 


238  INVESTIGATIONS  ON  THE  NERVOUS 

cases  of  fatal  chorea.  The  bacteriological  investigations  were 
negative,  but  in  both  cases  he  found  small  haemorrhages 
scattered  irregularly  throughout  the  brains  ;  there  were 
dilatation  of  blood-vessels  and  perivascular  exudation  of  cells. 
This  observer  also  found  fatty  changes  in  the  nerve  fibres  of 
the  brain  and  cord.  These  are  changes  such  as  would  be 
associated  with  an  infection  of  the  rheumatic  type.  The 
finding  of  such  local  lesions  to  some  extent  supports  the  view 
that  chorea  is  a  result  of  such  changes  rather  than  of  a  general 
cerebral  poisoning  by  the  toxins.  A  more  convincing  point  in 
the  pathology  of  chorea  would  be  the  demonstration  of  the 
diplococci  in  the  pia  mater  or  brain  in  cases  of  chorea.  Our 
opportunities  for  doing  this  have  been  few.  At  a  meeting  of 
the  Pathological  Society  in  December  1900  28  we  demonstrated 
diplococci  in  the  motor  cortex  of  a  case  of  very  severe  chorea, 
but  most  unfortunately  we  did  not,  when  we  made  the  necropsy, 
recognise  the  relation  of  the  diplococcus  to  rheumatism.  In 
both  our  recent  cases  alluded  to  here  we  found  them  in  the 
pia  mater  as  we  foretold  from  animal  experiment  in  1900 — 
viz.,  in  the  neighbourhood  of  the  capillary  blood-vessels. 
There  is  no  doubt  in  our  minds  that  the  destruction  of  these 
diplococci  in  the  pia  mater  must  be  rapid,  for  chorea  is 
a  lesion  comparable  to  rheumatic  arthritis  in  the  tendency 
to  complete  recovery,  and,  as  we  have  already  pointed  out, 
it  is  no  easy  task  to  find  them  in  acute  arthritis.  It  is, 
we  think,  encouraging  to  have  shown  a  diplococcus  in 
three  consecutive  cases  of  chorea  and  in  the  last  case  we 
know  that  this  diplococcus  can  produce  arthritis  and  peri- 
carditis in  rabbits  and  could  be  isolated  from  the  cerebro- 
spinal fluid. 

Lastly,  a  section  of  a  mitral  valve  from  a  case  of  early 
endocarditis  with  very  severe  chorea  illustrates  how  easily 
the  brain  could  be  infected  from  the  blood  stream,  vide 
Fig.  64.  These  have  been  our  only  opportunities  and 
neither  of  the  last  two  cases  should  we  have  chosen  for 
demonstration,  for  they  were  not  essentially  cases  of  fatal 
chorea  but  rather  fatal  pericarditis  with  chorea.  During 
the  last  five  years  we  have  never  had  an  opportunity  of 
investigating  one  of  the  rare  cases  of  fatal  chorea.  We 
have  not  attempted  lumbar  puncture  for  we  cannot  persuade 
ourselves  to  do  this  simply  for  purposes  of  investigation,  and 


e^HiM 


C^-;- 


«  FIG.  76 

Film  of  the  pia  mater  showing  :  A,  diplococci  in  the  pia  mater ;    B,  a  capillary 
blood-vessel.   From  a   case   of  fatal  rheumatic  pericarditis  with  chorea.     (Zeiss, 

Ohj.  T\r,  0C.    12.) 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    239 

our  views  upon  the  probability  of  success  of  this  method  are 
expressed  in  our  views  upon  arthritis.  In  spite  of  this,  the 
fact  that  we  have  succeeded  in  demonstrating  the  diplococcus 
in  cases  in  which  death  occurred  with  chorea  does,  we  believe, 
add  another  link  to  the  chain  of  evidence,  and  it  is  the  more 
suggestive  because  we  discovered  them  in  the  pia  mater  near 
capillary  blood-vessels  in  the  rabbit  which  showed  involuntary 
movements.29 

These  experimentally  produced  irregular  movements  need 
a  passing  mention.  Originally  described  by  ourselves  in  1900, 
we  then  in  a  very  guarded  manner  suggested  that  the  move- 
ments in  the  rabbit  were  analogous  to  chorea  in  a  child.  Meyer 
and  Beattie  independently  verified  the  occurrence  and  noticed 
twitching  movements.  Cole  later  produced  twitching  move- 
ments in  rabbits  by  the  injection  of  other  streptococci  and 
states  that  the  movements  had  no  resemblance  to  chorea.  In 
our  case  the  movements  were  of  that  type  and  entirely  different 
from  convulsive  movements  or  the  twitchings  of  a  dying 
animal  ;  in  fact,  we  killed  the  animal  in  order  to  demonstrate 
the  diplococci  in  the  brain  or  pia  mater.  The  search,  it  may 
be  added,  was  most  tedious  and  difficult,  as  might  be  supposed 
when  it  is  remembered  how  minute  is  the  size  of  this  diplococcus. 

To  summarise,  we  believe  that  eventually  rheumatic  chorea 
will  prove  to  be  a  local  infection  of  the  nervous  system  and 
that  most  of  its  symptoms  are  the  result  of  a  slight  meningo- 
encephalitis and  possibly  meningo-myelitis.  Our  reasons  for 
this  belief  are  :  (1)  We  have  isolated  and  cultivated  the 
diplococcus  from  the  cerebro-spinal  fluid  in  four  cases  of  fatal 
rheumatism,  in  three  of  which  there  was  chorea  at  the  time  of 
death.  (2)  We  have  produced  irregular  movements,  arthritis, 
endocarditis,  and  pericarditis  by  intravenous  injections  of  the 
diplococcus  into  rabbits.  (3)  We  have  demonstrated  the 
presence  of  diplococci  three  times  in  the  cerebral  pia  mater  and 
once  in  the  brain  from  chorea.  (4)  We  have  demonstrated 
them, in  the  brain  and  pia  mater  of  the  rabbit  that  had  shown 
the  irregular  movements. 

Part  III. — Rheumatic  Meningitis  (?) 

Our  last  case  is  a  most  interesting  one.  A  well-made  and 
intelligent  boy,  13  years  old,  was  admitted  into  University 


240  INVESTIGATIONS  ON  THE  NERVOUS 

College  Hospital  on  August  26,  1904,  suffering  from  arthritis 
of  the  ankles  and  knees  and  from  pain  across  the  chest  upon 
drawing  breath.  The  first  attack  of  pain  had  occurred  four 
days  before  his  admission,  the  ankles  had  commenced  to  swell 
three  days  before,  and  the  knees  upon  the  day  previous.  The 
family  history  showed  that  the  boy's  father  had  suffered  from 
rheumatic  fever  but  the  patient  himself,  except  for  an  attack 
of  measles  and  an  operation  for  adenoids,  had  enjoyed  excellent 
health.  His  condition  on  admission  appeared  to  be  a  very 
ordinary  attack  of  rheumatic  fever.  The  temperature  was 
103. 6°  F.  and  the  arthritis  was  of  the  usual  type,  the  heart 
was  dilated,  and  there  was  a  definite  systolic  mitral  murmur 
which  was  conducted  to  the  left  axilla.  Further,  rest  and 
salicylate  of  sodium  rapidly  reduced  the  temperature  and  by 
the  30th,  that  is  in  four  days,  all  pain  and  swelling  had  dis- 
appeared. From  that  date  until  September  17,  a  period  of  nearly 
three  weeks,  his  convalescence  was  uninterrupted,  while  in 
order  to  prevent  a  relapse  small  doses  of  salicylate  of  sodium 
were  continued.  On  the  17th,  without  any  apparent  cause, 
he  complained  of  headache  ;  he  was  sick,  and  his  temperature 
rose  to  102. 40  F.  The  next  day,  although  better  in  the 
morning,  he  again  vomited  in  the  afternoon  and  suffered  severe 
pain  in  his  head.  That  evening  he  was  drowsy  and  his  tempera- 
ture rose  again  to  102. 6°  F.  The  bowels  were  constipated  and 
for  this  reason  an  enema  was  given,  after  which  he  collapsed 
and  became  cyanosed  and  almost  pulseless.  At  8  a.m.  on  the 
19th  he  became  unconscious,  with  fixed  dilated  pupils  and 
general  muscular  rigidity,  alternating  with  naccidity.  His  skin, 
though  hot,  was  moist  ;  his  temperature  in  the  axilla  at  8  A.M. 
was  1010  F.,  and  at  n  a.m.  102. 40  F.  The  temperature  was 
now  taken  in  the  rectum  and  also  twice  with  different  thermo- 
meters in  the  groin  and  axilla.  In  the  rectum  the  temperature 
was  106. 40  F.  ;  in  the  other  situations  it  was  still  102. 40  F. 
All  efforts  at  treatment  were  fruitless  and  the  boy  died  comatose 
at  7.40  that  evening.  The  difference  in  the  temperature  in  the 
axilla  and  in  the  rectum  of  over  40  F.  is  remarkable  and  we 
believe  very  exceptional ;  in  fact,  if  the  rectal  temperature 
had  not  been  taken  the  hyperpyrcxial  element  in  the  illness 
would  certainly  have  escaped  notice.  The  clinical  aspect  of 
this  case  was  a  very  puzzling  one,  not  only  on  this  account  but 
because  the  symptoms  supervened  without  warning  at  a  time 


^\ 


EC      - 


/  * 


t 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    241 

when  all  believed  the  boy  was  quite  convalescent.  There  are, 
however,  other  cases  on  record  in  which  the  supervention  of 
cerebral  rheumatism  has  been  recorded  during  convalescence, 
and  it  is  well  known  that  this  condition  may  occur  when  the 
first  symptoms  of  rheumatism  are  slight  as  well  as  when  they 
are  severe.  The  most  probable  diagnosis  thus  appeared  to  be 
cerebral  rheumatism. 

The  necropsy  was  made  15  hours  after  death.  No  changes 
were  found  in  the  affected  joints.  There  was  a  slight  excess 
of  clear  fluid  in  the  pericardium  and  the  mitral  valve  showed 
early  endocarditis  in  the  process  of  healing.  There  was  also 
slight  pleuro-pericarditis  on  the  left  side  which  was  of  recent 
origin.  These  morbid  changes,  we  would  point  out,  were 
entirely  in  accord  with  the  occurrence  of  an  attack  of  recent 
acute  rheumatism.  In  no  part  of  the  body  could  any  focus  of 
suppuration  be  seen.  Examination  of  the  brain  showed  a 
condition  of  meningitis  almost  entirely  basal  in  distribution 
and  not  suppurative.  Except  that  it  is  spread  further  than  is 
usually  the  case  in  post-basic  meningitis,  the  appearance  was 
almost  identical  with  that  condition.  A  good  deal  of  turbid 
fluid  was  present  together  with  flakes  of  exudation  over  the 
medulla,  pons,  and  cerebellum.  There  was  also  a  general  spinal 
meningitis.  The  films  showed  minute  diplococci  in  numbers. 
And  we  would  point  out  that  even  in  this  extraordinary  and 
virulent  case  it  was  by  no  means  easy  to  find  the  micrococci  in 
the  pial  tissues. 

Cultures  were  taken  from  the  blood  in  the  heart,  the  peri- 
cardial and  cerebro-spinal  fluids,  and  brain.  The  cultures 
from  the  cerebro-spinal  fluid  contained  a  pure  growth  of  a 
diplococcus  in  bouillon  milk  and  glycerine  agar.  The  virulence 
of  these  cultures  was  higher  than  is  usually  the  case  with  the 
diplococcus  and  two  rabbits  inoculated  with  large  doses  died 
comatose  within  24  hours.  The  blood  film  showed  a  minute 
diplococcus  which  was  capsulated.  The  diplococcus  was 
isolated  from  the  blood  of  one  and  a  small  dose  was  injected 
intravenously  into  a  third  rabbit.  After  showing  some  loss  of 
health  this  animal  recovered.  Return  was  made  to  the  original 
culture  and  again  a  large  dose  produced  rapid  death,  but  a 
small  dose  was  recovered  from.  After  two  months  interval  a 
large  dose  was  again  used,  with  the  result  that  the  rabbit 
developed  arthritis  of  the  shoulder  joints  and  was  killed  in  the 

1G 


242  INVESTIGATIONS  ON  THE  NERVOUS 

convalescent  stage.     The  diplococcus  was  recovered  from  the 
damaged  joints. 

This  case  was  clinically  and  experimentally  very  exceptional 
and  we  have  only  brought  it  forward  as  a  contribution  to  the 
subject  of  meningitis  in  the  rheumatic.     Had  our  paper  been 
brought  forward  in  its  original  form  we  should  have  discussed 
the  various  explanations  of  the  case  and  the  details  of  its 
bacteriology,  but  to  do  so  now  would  be  out  of  place.     We 
bring  it  forward,  however,  because  we  are  inclined  to  the  belief 
that  it  was  a  true  rheumatic  meningitis  in  spite  of  the  fact  that 
we  observed  capsulation  of  the  diplococci  in  the  rabbit's  blood, 
which  we  admit  has  hitherto  been  regarded  as  a  distinguishing 
feature  of  the  pneumococcus.     In  any  case  it  is  worthy  of 
record  should  others  happen  upon  such  a  remarkable  condition. 
Lastly,    if    for  the   moment  this   case  is  accepted  as  a  true 
rheumatic  meningitis  the  question  arises  as  to  how  we  are  to 
link  together  these  three  remarkable  rheumatic  lesions  of  the 
brain  termed    (i)   rheumatic   chorea  ;     (2)   rheumatic   hyper- 
pyrexia or  cerebral  rheumatism  ;  and  (3)  rheumatic  meningitis. 
In  rheumatic  hyperpyrexia  the  rule  is  that  no  gross  macro- 
scopical  lesion  is  found.     Of  this  we  believe  there  is  no  doubt, 
for  we  have  referred  to  a  number  of  such  cases  since  the  time 
of  Fuller  and  have  again  and  again  found  the  same  record  of 
an  absence  of  gross  lesions.     Nevertheless,  recent  research  has 
shown  that  there  are  very  grave  microscopical  changes.     Thus 
Josue  and  Salomon  30  in  1903  found  in  such  a  case  diplococci 
in  the  pia  mater  and  in  some  of  the  cerebral  blood  capillaries, 
and  demonstrated  by  Nissl's  method  profound  changes  in  the 
nerve  cells  of  the  frontal  and  motor  cortex.     In  October  of  this 
year  Gandy  and  Borgnait  Legneule  31  in  a  rapidly  fatal  case 
found  diffuse  chromatolysis.     To  us,  then,  it  appears  that  this 
nervous  lesion  is  an  acute  rheumatic  toxaemia  in  contrast  to  the 
multiple  and  slight  local  lesions  we  believe  exist  in  chorea. 
Rheumatic   meningitis   we   would   place   between   these   two 
lesions,  because  there  is  on  the  one  hand  profound  poisoning 
and  on  the  other  a  severe  local  lesion.     Are  these  nervous 
lesions,  it  may  be  asked,  in  any  way  comparable  to  rheumatic 
lesions  of  other  organs  ?     We  believe  so,  and  would  venture 
the  following  comparison  : 

Mild  rheumatic  carditis  and  chorea. 

Severe  rheumatic  pericarditis  and  rheumatic  meningitis. 


MANIFESTATIONS  OF  ACUTE  RHEUMATISM    243 

Acute  fatal  rheumatic  cardiac  dilatation  and  acute  fatal 
rheumatic  hyperpyrexia. 

REFERENCES 

1  A  paper  read  before  the  Neurological  Society  of  the  United  Kingdom 
on  November  23,  1905. 

2  The  Lancet,  September  22  and  29,  1900. 

3  Klebs,  Archiv  fur  Experimentelle  Pathologie,  1875,  Band  IV,  p.  469. 
Wilson,  Edinburgh  Medical  Journal,  1885,  vol.  xxx,  p.  1105.  Mantle, 
"  The  Etiology  of  Rheumatism  from  a  Bacterial  Point  of  View,"  Brit. 
Med.  Jour.,  1887.  Popoff,  Meditz  Prebavlena  k'Morskomu  Sbomekie, 
1887,  p.  461.  Von  Leyden,  Congress  der  Innere  Medicin,  Berlin,  July  2, 
1894.  Triboulet  and  Coyon,  Comptes  Rendus  de  la  Societe  de  Biologie, 
1898,  p.  214.  Westphal,  Wassermann,  and  Malkoff,  Berliner  Klinische 
Wochenschrift,  1899,  No.  29,  &c. 

4  Poynton  and  Paine,  Transactions  of  the  Royal  Medical  and 
Chirurgical  Society,  1902. 

5  Transactions  of  the  Fourteenth  International  Congress  of  Medicine, 
Section  of  Medicine,  1903. 

6  Vernon  Shaw,  Journal  of  Pathology  and  Bacteriology,  December  1903. 

7  Ainley  Walker,  Practitioner,  1903. 

8  Beattie,  Brit.  Med.  Jour.,  December  1904. 

9  Loc.  cit.  10  Loc.  cit.  n  Loc.  cit. 

12  Predtetschensky,  Vratch,  1901,  No.  24. 

13  Fritz  Meyer,  Deutsche  Medicinische  Wochenschrift,  1901. 

14  Singer,  V erhandlungen  des  Congresses  fur  Innere  Medicin,  1897, 
1899. 

15  Allaria,  Rivista  Critica-de  Clinica  Medica,  1901,  No.  47. 

16  Jarvis,  TMse  de  Paris,  1902. 

17  Cole,  Journal  of  Infectious  Diseases,  vol.  i,  No.  4,  1904. 

18  Longcope,  American  Journal  of  the  Medical  Sciences,  1904. 

19  Herry,  La  Semaine  Medicate,  October  4,  1905. 

20  Philipp,  Deutsches  Archiv  fur  Klinische  Medicin,  Band  LXX, 
Hefte  1-3. 

21  Walker  and  Ryffel,  Brit.  Med.  Jour.,  September  19,  1903. 

22  Gordon,  Lancet,  November  11,  1905,  p.  1400. 

23  Dana,  American  Journal  of  the  Medical  Sciences,  1894,  p.  31. 

24  Apert,  Societe  de  Biologie,  January  20,  1898. 

25  Poynton  and  Paine,  Transactions  of  the  Fourteenth  International 
Congress  of  Medicine,  Section  of  Pediatrics,  1903. 

26  Poynton  and  Shaw,  Transactions  of  the  Pathological  Society,  1904. 

27  Reichart,  Deutsches  Archiv  fur  Klinische  Medicin,  1902,  p.  504. 

28  Poynton  and  Paine,  Transactions  of  the  Pathological  Society,  1901. 

29  Poynton  and  Paine,  "  Some  Further  Investigations  upon  Rheumatic 
Fever,"  Lancet,  May  4,  1901,  p.  1260. 

30  Josue  and  Salomon  at  a  meeting  of  the  Paris  Hospitals  Medical 
Society,  July  25,  1905. 

31  Gandy  and  Borgnait  Legneule  at  a  meeting  of  the  Hospitals 
Medical  Society,  Paris,  October  27,  1905. 


PAPER  NO.  XIX 

A  CONTRIBUTION  TO  THE  PATHOLOGY 
OF  CHOREA 

By  Dr.  F.  J.  POYNTOX  and  Dr.  W.  GORDON  HOLMES 
(Reprinted  from  the  Lancet,  October  13,  1906.) 

The  collaboration  of  Dr.  Gordon  Holmes,  then  Director  of  the  Nervous 
Disease  Research  Fund  at  the  National  Hospital  for  the  Paralysed 
and  Epileptic,  enabled  us  in  this  paper  to  study  the  minute  pathology 
of  chorea  by  the  most  recent  methods  of  that  date.  The  number  of  cases 
of  fatal  chorea  that  were  investigated  was  increased  and  a  detailed 
explanation  of  the  occurrence  of  rheumatic  chorea  given  in  the  light  of 
the  changes  that  were  found  in  the  nervous  system.  In  addition,  a 
study  of  a  case  of  chorea  occurring  in  pregnancy  enabled  us  to  discuss 
the  nature  of  this  condition,  which,  in  accord  with  the  experience  of 
other  investigators,  we  believed  to  be  frequently  rheumatic  in  nature. 

In  the  present  communication  we  are,  firstly,  adding  three 
more  to  the  recorded  observations  of  the  presence  of  a  diplo- 
coccus  in  the  pia  mater  of  cases  that  have  proved  fatal  while 
suffering  from  chorea.  In  addition,  this  micro-organism  has 
been  demonstrated  in  the  brains  of  these  cases  lying  in  the 
perivascular  spaces  and  connective  tissue.  Secondly,  we  have 
also  studied  by  the  most  recent  methods  the  two  series  of 
changes — viz.,  those  affecting  the  connective  and  vascular 
tissues  and  those  which  occur  in  the  nervous  tissues  in  chorea. 
And,  lastly,  we  have  demonstrated  that  in  a  case  of  chorea 
which  occurred  in  a  first  pregnancy  lesions  were  present 
similar  to  those  that  were  found  in  the  rheumatic  cases.  Such 
opportunities  could  never  have  offered  themselves  if  it  had  not 
been  for  the  kindness  of  Sir  Cooper  Perry  and  Dr.  H.  S.  French, 
Dr.  J.  Rose  Bradford  and  Dr.  H.  Batty  Shaw,  and  we  are 
greatly  indebted  to  them  for  the  pathological  material  and 
permission  to  use  the  clinical  and  post-mortem  notes  of  these 
cases.     Deaths  from  chorea  are  so  rare  that  the  opportunities 

244 


PATHOLOGY  OF  CHOREA  245 

for  testing  the  results  in  several  cases  at  short  intervals 
are  most  exceptional,  but  through  their  kindness  these 
three  cases  came  to  us  within  a  month  and  gave  us  an 
opportunity  of  repeating  and  comparing  our  observations. 

The  Clinical  Cases 

Case  i.  Our  first  case,  for  which  we  are  indebted  to 
Dr.  Shaw,  was  that  of  a  girl  aged  seven  years,  who  was 
admitted  to  the  Children's  ward  at  University  College  Hospital 
on  March  25,  1906.  Her  illness  had  commenced  three  weeks 
previously  with  multiple  arthritis,  ushered  in  with  acute 
malaise  and  vomiting.  After  a  temporary  improvement 
chorea  and  pericarditis  developed,  and  when  admitted  her 
condition  was  hopeless.  Death  occurred  two  days  later  from 
heart  failure,  the  chorea  having  lasted  about  17  days.  While 
under  observation  the  temperature  ranged  between  1040  and 
990  F.,  the  chorea  was  very  severe,  the  pericarditis  was  general, 
and  valvular  disease  was  also  present.  In  her  previous  history 
there  was  a  record  of  an  attack  of  rheumatic  fever  at  five  years 
of  age.  The  post-mortem  examination  showed  general  and 
recent  pericarditis,  bilateral  pleurisy,  mitral  endocarditis,  and 
myocarditis. 

This  case  was  one  of  extreme  severity  and  illustrates  a 
difficulty  that  has  to  be  reckoned  with  in  studying  chorea. 
During  the  last  week  of  life  blebs  full  of  serous  fluid  developed 
upon  the  back  and  elsewhere  and  the  incessant  movements 
rapidly  converted  them  into  open  sores.  An  occurrence  such 
as  this  must,  we  readily  admit,  introduce  the  question  of 
secondary  infection  and  increase  the  difficulties  of  an  accurate 
interpretation  of  any  results.  For  our  own  part  we  are 
sceptical  that,  under  these  conditions,  a  secondary  infection 
will  explain  the  results  of  post-mortem  investigation,  because 
it  has  been  repeatedly  demonstrated  that  in  acute  rheumatism 
similar  bacteriological  results  to  those  we  obtained  on  this 
occasion  can  be  shown  when  there  is  no  question  at  all  of 
open  sores. 

There  is  yet  another  point  of  interest  about  this  case. 
Some  eminent  bacteriologists  dispute  any  direct  association 
between  the  diplococcus  and  acute  rheumatism  and  some 
have  failed  to  find  the  micrococcus  after  repeated  search  in 
cases  of  rheumatism.     In  this  case,  however,  a  pure  growth 


246  A  CONTRIBUTION  TO  THE 

of  a  diplococcus  was  obtained  from  the  heart's  blood  by 
Dr.  F.  H.  Thiele,  clinical  pathologist  to  University  College 
Hospital.  Its  presence  was  demonstrated  in  the  pericardium  by 
Dr.  T.  Lewis,  the  house  plrysician  to  the  case.  It  was  again  de- 
monstrated by  one  of  us  in  the  pia  mater  and  by  another  in  the 
brain,  and  was  cultivated  by  Dr.  Paine,  and  on  experimental 
injection  into  animals  produced  multiple  arthritis  and  peri- 
carditis of  the  usual  type.  It  will  be  seen,  then,  that  five 
different  observers  independently  recognised  the  occurrence  of 
a  diplococcus  in  this  case,  which  had  the  features  of  the 
diplococcus  described  in  rheumatism. 

Pathological  investigation.     Only  the  right  half  of  the  brain, 
brain-stem,  and  cerebellum  and  a  portion  of  the  diseased  heart 
valve  were  received  for  examination.     Macroscopical  examina- 
tion.    The  vessels  of  the  meninges  and  cortex  of  the  hemisphere, 
and  to  a  less  extent  those  of  the  membranes  on  the  base  of  the 
brain  and  brain-stem,  were  very  much  engorged.     No  exuda- 
tion or  signs  of  inflammation  were  visible  to  the  naked  eye,  but 
several    small    subpial    haemorrhages    could    be    seen    on    the 
convexity    of    the    hemisphere.     Microscopical    examination. 
Sections  stained  with  hematoxylin  revealed  great  congestion 
of  the  blood-vessels  of  the  membranes  and  of  the  brain  itself, 
and  in  many  places  small  haemorrhages  were  visible,  especially 
on  the  under  surface  of  the  pia  mater.     A  small  proportion  of 
the  vessels  of  the  pia-arachnoid,  generally  the  smaller  arteries, 
were  thrombosed,  especially  over  the  convexity  of  the  hemi- 
sphere, and  there  was  in  places  definite  evidence  of  serous 
exudation  and  small  round  cell  infiltration  into  the  membranes 
in  the  immediate  neighbourhood  of  the  vessels.     Thrombosed 
vessels  were  still  more  common  in  the  cortex  and  subcortical 
white  matter,  but  in  the  majority  the  clots  seemed  to  be  quite 
recent,  though  some  were  partially  organised.     Thrombosed 
vessels  could  be  occasionally  followed  into,  or  found  within, 
small  patches  of  softening,  which  lay  most  frequently  in  the 
deeper  layers  of  the  cortex.     The  destruction  of  tissue  within 
them   was   never   complete  ;    there   was   considerable   serous 
exudation  into  the  recent  ones,  while  the  older  were  marked 
by  proliferation  of  neuroglial  nuclei  and  sclerosis.     There  was 
also  small  round  cell  infiltration  into  the  sheaths  and  peri- 
vascular spaces  of  many  of  the  vessels  which  were  not  throm- 
bosed and  a  polymorphonuclear  leucocyte  was  occasionally  seen 


PATHOLOGY  OF  CHOREA  247 

among  them.  These  changes  were  equally  marked  over  the 
whole  hemisphere  and  within  the  basal  ganglia,  but  no  foci  of 
necrosis  were  observed  in  the  cerebellum,  pons,  or  medulla, 
though  here,  too,  there  was  considerable  congestion  of  the  vessels 
and  frequently  small  round  cell  infiltration  into  their  sheaths. 
When  the  brain  was  examined  by  Nissl's  method  definite 
cell  changes  were  found,  which  were  greater  in  the  cerebral 
cortex  than  in  any  other  part  of  the  central  nervous  system. 
Practically  all  the  cortical  cells  were  affected  ;  as  a  rule  they 
were  swollen  and  distended,  their  tigroid  had  partly  disappeared 
so  that  they  stained  diffusely  or  occasionally  almost  uniformly, 
and  their  nuclei,  which  were  swollen  and  excentrically  situated 
in  a  certain  number  of  the  cells,  stained  more  deeply  than 
normal.  The  nucleoli  appeared  unaltered  and  the  cell  pro- 
cesses seemed  normal  except  that  they  were  not  easily  visible 
owing  to  diminution  of  their  chromatophilic  substance.  The 
degree  of  affection  of  the  large  Betz  cells  was  very  variable. 
In  the  majority  there  was  only  slight  chromatolysis  immediately 
around  the  nucleus  where  the  Nissl  bodies  were  broken  up 
into  a  deeply  staining  granular  material,  while  they  remained 
normal  in  the  periphery  of  the  cell  and  in  the  dendrites.  In 
the  next  stage  there  was  more  extensive  perinuclear  chroma- 
tolysis and  the  nuclei  were  more  generally  swollen  and  more 
frequently  excentric.  A  small  number  of  cells  were  still 
more  severely  affected  ;  their  outlines  were  scarcely  recognis- 
able, their  nuclei  were  shrunken  and  deformed,  and  no  stain- 
able  substance  was  visible  in  them.  The  cells  of  the  basal 
ganglia  were  less  affected  ;  there  was  at  the  most  only  evidence 
of  commencing  chromatolysis  and  slight  swelling  of  the  nuclei. 
The  cells  of  the  different  portions  of  the  brain-stem  were  in 
much  the  same  state  ;  they  stained  rather  faintly  and  there 
was  commencing  disintegration  of  their  tigroid  masses.  No 
definite  changes  were  recognised  in  the  cells  of  the  cerebellum. 
Various  portions  of  the  forebrain  and  brain-stem  were  treated 
by  Marc  hi 's  method.  A  few  degenerated  fibres  were  found  on 
the  borders  and  neighbourhood  of  the  small  patches  of  soften- 
ing, but  there  was  otherwise  no  evidence  of  disease  in  the 
cortex  except  in  the  presence  of  dark  granular  masses  in  the 
perivascular  spaces  or  in  the  walls  of  the  blood-vessels,  which 
probably  represented  the  process  of  removal  of  some  degenerate 
products. 


248  A  CONTRIBUTION  TO  THE 

Bacteriological  examination.  Thin  films  of  pia  mater  were 
stripped  off  the  brain,  fixed  on  slides,  and  hardened  in  alcohol. 
They  were  then  stained  by  Loffier's  methylene  blue  and 
examined  under  an  oil-immersion  lens.  In  other  places  the 
pia  mater  was  cut  along  with  the  brain  it  covered  in  paraffin 
and  stained  by  the  same  method.  On  careful  search  bacteria 
were  found  in  the  pia  mater  ;  the  majority  appeared  as 
isolated  diplococci  of  small  size,  but  frequently  larger  groups 
of  micrococci,  many  of  which  lay  in  pairs,  were  visible,  and 
occasionally  a  single  micrococcus  was  also  seen.  The  morpho- 
logical characters  of  the  micrococci  were  in  every  place  the 
same  ;  they  were  remarkably  small  on  the  whole  but  rather 
irregular  in  size.  No  other  bacteria  were  found  in  the  meninges. 
Similar  diplococci  were  found  in  sections  of  the  brain  which  had 
been  cut  in  paraffin  and  stained  in  the  same  way.  They 
were  seen,  however,  only  in  the  loose  connective  tissue  sur- 
rounding the  vessels  and  in  the  perivascular  spaces  ;  despite 
careful  search  none  were  discovered  in  the  brain  tissue.  Their 
presence  did  not  seem  to  bear  any  relation  to  the  intensity  of 
the  vascular  changes  or  to  the  presence  of  thrombosis,  but 
infiltration  by  small  round  cells,  evidently  of  vascular  origin, 
was  generally  visible  in  their  neighbourhood  both  in  the 
meninges  and  in  the  brain.  Groups  of  similar  micrococci  were 
found  in  the  ulcerated  heart  valve.  Here  they  generally  lay 
in  groups  in  which  the  diplococcic  arrangement  was  readily 
visible,  most  frequently  at  the  junction  of  the  necrotic  and 
inflammatory  tissue,  but  in  places  they  extended  to  the  surface 
of  the  ulcers  or  vegetations.  Similar  diplococci  were  present 
in  the  inflammatory  tissue  in  the  pericardium.  Morphologically 
these  micrococci  seemed  identical  with  those  found  in  the 
meninges.  Dr.  Paine  kindly  investigated  for  us  the  cultures 
obtained  by  Dr.  Thiele  from  the  blood  in  the  left  ventricle  and 
found  that  intravenous  injection  into  the  auricular  veins  of 
rabbits  produced  arthritis  and  pericarditis. 

Case  2.  The  second  case,  a  boy  aged  14  years,  was 
admitted  to  University  College  Hospital,  under  the  care  of 
Dr.  Bradford,  on  May  8,  1906.  He  had  been  ill  for  two 
months  and  in  his  past  history  there  was  a  record  of  several 
attacks  of  subacute  rheumatism.  The  first  symptoms  of  the 
present  illness  began  with  pains  all  over  the  body,  and  for 
some  weeks  before  admission  he  had  developed  prsecordial 


»<*r   * 


I 


■:-      if 


WJ 


i 

v.  ■■ 

K. 


i*l\{ 

!*»! 


4. 


■ 


FIG.   79 

man  chorea.  Reproduction  of  a  microphoto- 
ph  showing  small   round-cell    infiltration 
-y  the  sheath  and  perivascular  space  of  a 
vessel  iu  the  subcortical  white  matter. 


FIG.   80 

Two  large  pyramidal  cells  and  three  Betz  cells  from  the  precentral 
convolution  of  Case  1.     Showing  various  degrees  of  chromatolysis. 


■j*-.:v 

4m 


*.> 


<& 


m 


*& 


FIG.  81 

Human  chorea.   Section  of  a  vegetation  on  the  mitral  valve  showing  the  presence  of 
diplococci      ((  ase  3.) 


PATHOLOGY  OF  CHOREA  249 

pain,  cough,  and  dyspnoea.  His  condition  was  critical.  On 
admission  the  temperature  was  1020  F.,  the  pulse-rate  was 
120,  and  the  respiration  was  28  to  the  minute.  The  heart 
was  rapid  and  excited,  with  a  loud  apical  systolic  murmur. 
There  were  crepitations  at  the  bases  of  both  lungs  and  the 
mental  state  was  dull.  After  he  had  been  a  few  days  in  the 
hospital  the  excited  action  of  the  heart  suggested  pericarditis 
in  spite  of  the  fact  that  there  was  no  pericardial  friction.  In 
addition,  patches  of  penumonia  had  now  developed.  On  the 
13th  the  boy  was  actively  delirious  and  chorea  commenced 
and  rapidly  became  violent.  Death  occurred  on  the  nine- 
teenth day,  the  temperature  to  the  end  never  becoming 
hyperpyrexial.  This  case  is  of  exceptional  value  because  the 
chorea  developed  under  observation. 

The  necropsy  showed  that  there  was  recent  pericarditis 
over  the  posterior  surface  of  the  heart.  The  pericardium  was 
adherent  over  the  front  and  there  was  recent  endocarditis  of 
the  mitral  and  tricuspid  valves.  The  lungs  were  in  a  condition 
of  acute  oedema. 

Pathological  investigation.  Only  the  brain  and  brain-stem 
were  received.  Examination  revealed  a  condition  so  similar 
to  that  of  Case  1  that  but  little  additional  description  is 
needed.  Macroscopical  examination.  To  the  naked  eye  the 
state  of  the  brain  was  identical  with  that  of  Case  1.  There 
was  a  similar  engorgement  of  the  vessels  with  subpial  haemor- 
rhages. Microscopical  examination.  As  in  the  previous  case, 
the  engorgement  of  the  vessels  was  a  very  prominent  feature 
in  sections  of  the  membranes  and  brain.  Very  few  of  the 
vessels  were,  however,  thrombosed  and  only  two  small  and 
incomplete  patches  of  softening  were  found  though  a  large 
number  of  sections  were  examined.  Many  of  the  vessels 
contained  large  masses  of  leucocytes  and  there  was  in  places 
considerable  oedema  in  the  perivascular  spaces  and  the  brain 
tissue  around  them.  In  this  case,  on  the  other  hand,  there 
was  jxiore  cellular  infiltration  into  the  meninges  and  into  the 
sheaths  and  perivascular  spaces  of  the  cerebral  vessels.  The 
use  of  Nissl's  method  revealed  similar  changes  in  the  nerve 
cells,  greatest  in  the  cortex,  and  approximately  equal  in  all  its 
regions.  In  this  case,  too,  the  nerve  cells  of  the  basal  ganglia 
and  brain-stem  were  less  affected  than  the  cortical  cells.  No 
degenerated  medullated  fibres  were  made  visible  by  Marchi's 


250  A  CONTRIBUTION  TO  THE 

method,  but  irregular  masses,  which  stained  dark  by  osmic 
acid,  similar  to  those  in  Case  I,  were  found  in  the  perivascular 
spaces  of  the  brain. 

Bacteriological  examination.  The  examination  was  con- 
ducted in  the  same  way  as  in  Case  I  and  yielded  similar 
results.  The  diplococci  were,  however,  more  numerous  in  the 
meninges  of  this  case  and  groups  of  similar  micrococci  were 
easily  found  in  the  adventitial  sheaths  and  perivascular  spaces 
of  the  brain.  Neither  the  heart  valves  nor  pericardium  were 
received  for  examination. 

Case  3.  For  the  third  case  we  are  indebted  to  the  kindness 
of  Sir  Cooper  Perry  and  Dr.  French.  This  was  a  case  of 
chorea  occurring  in  a  first  pregnancy  without  a  previous 
history  of  chorea  or  rheumatism.  It  is  clear  that  the  inter- 
pretation of  any  of  the  results  that  we  have  obtained  in  this 
case  must  be  made  with  minds  alive  to  possible  fallacies.  We 
shall  on  this  account  plainly  state  that  the  results  are  put  on 
record  as  facts  observed  in  a  single  case  only  and  the  inter- 
pretation put  upon  these  facts  is  left  open  to  free  criticism. 
The  history  of  the  case  was  published  by  Dr.  French  and 
Mr.  H.  T.  Hicks  1  and  is  as  follows. 

"  R.  D.,  aged  21,  had  been  married  four  months  and  was 
pregnant  at  the  second  month  for  the  first  time. 

"  History.  She  had  had  no  previous  chorea  nor  acute 
rheumatism.  The  present  chorea  began  at  the  second  week 
of  pregnancy.  The  movements  were  slight  at  first  and  got 
worse  gradually.  On  admission  she  was  so  violent  and  noisy 
that  she  had  to  be  taken  to  the  strong  room.  Nasal  feeding 
was  resorted  to,  the  choreic  movements  being  controlled  by 
chloroform.     She  was  emaciated.     There  was  no  bruit. 

"  Result.  The  uterus  was  evacuated  after  rapid  dilatation 
under  chloroform  ;  the  patient  seemed  quieter  next  day.  The 
chorea  ceased  but  the  patient  became  collapsed  and  died  on 
the  fifth  day  after  the  uterus  was  emptied. 

"  Autopsy.  There  were  recent  vegetations  all  along  the 
mitral  valve  ;  there  were  no  infarcts.  Cultivations  of  the 
heart  blood  showed  bacillus  coli  communis  only.  Cultivations 
from  the  spleen  remained  sterile  after  incubation  for  three 
days  at  370  C." 

A  most  interesting  feature  in  this  case,  which,  as  we  have 
just   pointed  out,  gave  no  personal  history  of  rheumatism, 


PATHOLOGY  OF  CHOREA  251 

was  the  condition  of  the  mitral  valve.  This  valve  showed  a 
row  of  early  vegetations  which  were  indistinguishable  from 
those  on  the  valve  in  Case  1,  which  was  the  result  of  an  obvious 
and  exceedingly  active  attack  of  acute  rheumatism.  These 
two  valves  were  sent  to  us  in  the  same  week,  and  their  resem- 
blance was  most  striking  ;  nor  did  the  resemblance  cease  here, 
for  on  section  we  found  that  the  valve  from  the  case  in  which 
there  was  no  personal  history  of  rheumatism  and  the  valve 
from  the  active  rheumatism  both  contained  diplococci  similar  in 
appearance  and  distribution,  and  both  showed  tissue  changes  of 
similar  nature. 

Pathological  investigation.  Only  the  brain  and  brain-stem 
and  portions  of  the  ulcerated  cardiac  valves  were  obtained. 
Macroscopical  examination.  To  the  naked  eye  the  brain  was 
similar  to  that  of  the  other  two  cases,  but  there  was  less 
vascular  engorgement.  Microscopical  examination.  Vascular 
engorgement  of  the  brain  and  its  membranes  was  also  a 
prominent  feature  in  this  case,  but  only  very  few  thrombosed 
vessels  could  be  found  and  in  all  these  the  clots  appeared  to  be 
quite  recent.  None  were  fully  organised  and  there  were  no  such 
changes  in  their  intima  as  would  have  resulted  from  long  occlu- 
sion. No  definite  patches  of  softening  were  found,  though  around 
some  of  the  thrombosed  vessels  the  brain  tissue  was  slightly 
necrotic  and  infiltrated  by  serum.  There  was  also  here  less  small 
round  cell  infiltration  into  the  walls  and  perivascular  spaces 
of  the  cerebral  vessels,  though  in  places  it  was  quite  marked. 

While  the  changes  in  the  vascular  system  were  less  in 
degree,  though  similar  in  kind,  in  this  case  than  in  the  two 
above  described,  the  affection  in  the  nerve  cells  was  consider- 
ably greater.  In  scarcely  one  of  the  cortical  cells  was  tigroid 
visible  in  the  form  of  ordinary  Nissl  bodies  ;  the  protoplasm 
stained  diffusely  or  almost  uniformly  and  generally  darker 
than  normal.  The  nuclei  were  definitely  enlarged,  especially 
those  of  the  large  pyramidal  cells  and  the  Betz  cells,  but  the 
nuclear  chromatin  remained  as  a  rule  easily  visible  in  a  pale 
ground  and  apparently  unaltered.  In  other  cells,  however, 
the  nuclei  retained  so  much  stain  as  to  make  them  appear 
dark  and  almost  homogeneous  ;  these  nuclei  were  often 
smaller  than  normal  and  occasionally  irregular  in  shape.  In 
some  cells,  especially  in  the  Betz  cells,  the  nuclei  were  excentric, 
but  in  the  majority  they  remained  central.     No  pathological 


252  A  CONTRIBUTION  TO  THE 

changes  were  observed  in  the  nucleoli.  Some  of  the  affected 
cells,  especially  the  larger  ones,  were  considerably  shrunken. 
These  changes  were  equally  marked  in  all  parts  of  the  cerebral 
cortex.  The  cells  of  the  corpus  striatum  and  of  the  thalamus 
were  practically  identically  affected  ;  no  absolutely  normal 
cell  was  found  in  them.  Some  were  considerably  swollen  and 
all  stained  so  diffusely  that  no  clumps  of  tigroid  could  be 
distinguished  either  within  them  or  their  dendrites.  The  cell 
changes  were  less  pronounced  in  the  pons  and  medulla  ;  the 
cells  of  the  motor  nuclei  had  undergone  relatively  slight 
tigrolysis  and  had  merely  a  punctate  appearance,  due  to 
fragmentation  and  partial  absorption  of  the  Nissl  bodies. 
None  of  them  were  swollen  and  their  nuclei  were  as  a  rule 
normal.  The  cells  of  the  sensory  nuclei  and  of  the  rest  of  the 
grey  matter  of  the  pons  and  medulla  were  somewhat  similarly 
affected.  The  Purkinje  cells  of  the  cerebellum  were  only  very 
slightly  affected,  but  those  of  the  nucleus  dentatus  had  suffered 
more  severely  ;  the}7  were  swollen,  their  nuclei  often  lay 
excentric,  and  in  the  majority  there  was  complete  disappear- 
ance of  the  Nissl  bodies.-  No  degenerated  fibres  were  found  on 
examination  by  Marchi's  method,  but  many  of  the  medullated 
fibres  of  the  forebrain  were  coloured  a  faint  brownish  tint, 
probably  representing  a  slight  chemical  change  in  the  myeline. 
The  same  evidence  of  degeneration  products  was  visible  in  the 
perivascular  spaces  and  vessel  walls  as  in  the  other  two  cases. 

Bacteriological  examination.  Micrococci,  generally  lying  as 
diplococci  and  identical  in  appearance  with  those  described  in 
Cases  i  and  2,  were  found  after  careful  searching  in  the  pia 
mater  of  the  forebrain  and  in  the  walls  of  the  cerebral  vessels. 
They  were  infrequent  in  the  portions  of  tissue  examined,  but 
quite  as  numerous  as  in  Case  1.  Similar  diplococci  were  also 
found  in  the  diseased  heart  valve,  in  the  same  position  as  in 
Case  1. 

Part  III. — The  Pathology  of  Chorea 

It  now  remains  to  interpret  the  results  that  were  obtained 
in  these  three  cases  :  firstly,  in  their  bearing  upon  the  nature 
of  chorea  ;  and,  secondly,  with  reference  to  the  relationship 
of  chorea  and  rheumatism. 

I.  The  nature  of  chorea.  In  considering  the  changes  de- 
scribed   as    the    anatomical    substratum    of    chorea    we    are 


a 


i 


Y* 


- 


FIG.  82 

Human  chorea.    Film  of  the  pia  mater  showing  the  presence  of  two 
groups  of  diplococci. 


€ 


FIG.  83 

Human  chorea.   Section  of  cerebral  cortex  showing-  (a)  the  presence  of 

diplococci   in,  and  cell  infiltration  of,  the  adventitial  sheath  of  a 

vessel. 


PATHOLOGY  OF  CHOREA  253 

unhappily  limited  by  the  fact  that  in  none. of  the  three  cases 
was  the  spinal  cord  obtained  for  examination.  Yet  this 
restriction  is  not  serious,  for  though  definite  pathological 
changes  would  probably  have  been  found  there,  as  in  every 
other  part  of  the  central  nervous  system,  it  would  be  im- 
possible to  assume  that  the  cord  played  any  great  part  in 
the  production  of  the  choreal  movements.  For,  quite  apart 
from  the  distribution  of  the  movements,  their  nature  makes 
it  highly  improbable  that  they  arise  in  the  spinal  cord.  To 
quote  Dr.  J.  Hughlings  Jackson,  "  these  movements  are  not 
mere  spasms  and  cramps,  but  an  aimless  profusion  of  move- 
ments, of  considerable  complexity,  much  nearer  the  purposive 
movements  of  health,"  2  and  therefore  "it  is  certain  that  the 
part  diseased  serves  in  highly  special  and  complex  coordina- 
tions, and  that  thus  it  is  a  part  very  high  up  in  the  nervous 
system."  3 

The  study  of  the  central  nervous  system  has  shown  that 
the  pathological  changes  which  form  the  morbid  anatomy  of 
the  disease  are  composed  of  (1)  vascular  and  inflammatory 
changes  in  the  central  nervous  system  and  its  membranes  ; 
and  (2)  changes  in  the  nervous  tissue  itself,  consisting  of 
destructive  lesions  secondary  to  the  vascular  changes  and  of 
alterations  in  the  morphological  characters  of  the  nerve  cells. 

The  most  prominent  vascular  change  in  all  three  cases  was 
the  great  hyperemia  of  all  parts  of  the  brain  and  the  presence 
of  thrombosed  vessels  ;  the  latter  were  rather  numerous  in 
Case  1  but  more  rarely  seen  in  Cases  2  and  3.  Whether  the 
thrombi  were  primary  or  secondary  to  embolism  is  impossible 
to  say,  but  no  emboli  were  seen  in  the  sections  which  were 
studied.  In  Case  1  patches  of  softening  were  found  associated 
with,  and  evidently  a  result  of,  these  vascular  occlusions,  but 
they  were  very  infrequent  and  rarely  pronounced  in  degree  in 
Cases  2  and  3.  But  more  constant  in  all  three  cases  was  the 
evidence  of  inflammatory  reaction  shown  by  the  presence  of 
perivascular  small  round  cell  infiltration  and  serous  exudation 
around  'the  vessels.  The  consideration  of  these  changes  is 
interesting  in  relation  to  the  theory  of  Kirkes,  which  was 
supported  by  Hughlings  Jackson  4  and  Broadbent,;  that  they 
are  the  serological  factors  of  the  choreal  movements.  According 
to  Dr.  Hughlings  Jackson  it  is  apparent  that  the  disorder  of 
function  must  arise  from  instability  and  overaction    of    the 


254  A  CONTRIBUTION  TO  THE 

nerve  tissue,  which  he  explains  by  the  increase  of  nutrition  due 
to  the  collateral  hyperaemia  that  results  from  vascular  occlusion 
by  embolism,  assuming,  of  course,  that  only  the  smallest 
vessels  are  occluded.  Ingenious  though  this  theory  is,  it  is 
hardly  acceptable  on  the  evidences  afforded  by  the  investiga- 
tion of  our  three  cases,  for  though  hyperaemia  was  very  pro- 
nounced there  was,  in  two  of  the  cases  at  least,  very  little 
evidence  of  embolism  on  microscopical  examination.  It  seems 
to  us  that  there  is  a  more  definite  reason  for  the  congestion  of 
the  vessels  which  we  shall  consider  below.  Further,  in  view  of 
the  pronounced  cell  changes  and  the  presence  of  micro- 
organisms in  the  brain  and  its  membranes,  other  possible 
factors  must  be  considered.  The  foci  of  necrosis,  we  would 
add,  may  be  neglected  in  seeking  the  causal  agent,  as  they 
are  purely  destructive  lesions  and  cannot,  therefore,  directly 
produce  active  or  positive  symptoms. 

As  the  nerve  cells  of  one  or  several  regions  must  be  the 
direct  agent  in  production  of  the  movements  the  changes 
found  in  them  are  important  and  claim  our  first  consideration. 
At  first  the  question  arises,  What  is  the  significance  of  these 
changes  ?  Under  what  conditions  are  they  known  to  develop  ? 
The  changes  are  those  described  by  the  term  chromatolysis  ; 
they  consist  of  partial  solution  of  the  stainable  substance  of 
the  cell  and  slight  alteration  in  the  appearance  or  even  position 
of  the  cell  nucleus  ;  in  some  of  the  cortical  cells,  especially  in 
Case  3,  the  changes  had  advanced  further,  and  both  the  bodies 
and  nuclei  of  the  cells  stained  deeply  and  homogeneously  as 
though  they  had  undergone  coagulation  necrosis.  These 
changes  represent  a  vital  reaction  of  the  cell  to  some  abnormal 
influence.  It  is  known  that  chromatolysis  is  found  in  cells 
which  have  been  subjected  to  overwork,  but  the  possibility  of 
over-activity  being  the  cause  in  these  cases  may  be  at  once 
rejected,  for  the  cell  changes  were  universal  throughout  the 
brain  and  brain-stem,  that  is,  they  occurred  in  some  groups  of 
cells  which  it  is  groundless  to  assume  were  over-active.  In 
the  cells  of  the  motor  area,  however,  and  especially  in  the  Betz 
cells,  over-activity  may  have  had  a  part  in  the  pathogenesis 
of  the  changes.  They  were  certainly  not  the  result  of  pyrexia, 
for  the  pyrexia  in  these  cases  was  not  considerable,  with  the 
exception  of  the  last  few  days  of  life  in  the  case  of  chorea  of 
pregnancy. 


PATHOLOGY  OF  CHOREA  255 

The  assumption  that  the  changes  described  are  due  to  the 
action  of  bacterial  toxins,  on  the  other  hand,  is  suggested 
by  the  frequent  association  of  chorea  with  the  undoubtedly 
infective  condition  known  as  rheumatism,  and  by  the  discovery 
of  micro-organisms  in  the  central  nervous  and  vascular  systems, 
both  by  ourselves  and  other  workers.  This  view  is  compatible 
with  the  results  of  examination  of  the  nerve  cells  in  other 
infective  diseases — e.g.,  diphtheria,  typhoid  fever,  and  septi- 
caemia, where  analogous  changes  have  been  found  (Babes, 
Marinesco,  and  others).  The  assumption  of  a  bacterial  toxin 
(whether  specific  or  not  matters  not)  explains  also  the  local 
vascular  disturbances,  which  may  be  regarded  as  a  reaction  to 
its  presence,  the  occurrence  of  degeneration  products  in  the 
walls  of  the  vessels  and  the  evidence  of  the  slight  chemical 
change  revealed  by  Marchi's  method  in  the  medullated  fibres 
of  Case  3. 

If  it  is  accepted  that  the  action  of  a  toxin  is  the  immediate 
agent  in  the  causation  of  choreal  movements  the  question 
then  naturally  arises,  if  chorea  is  cerebral  rheumatism  in  the 
sense  that  it  is  produced  by  the  same  bacterial  poisons  which 
giye  rise  to  the  symptoms  of  ordinary  acute  rheumatism,  is  it 
necessary  that  there  should  be  infection  of  the  brain  and  its 
membranes  by  the  bacteria,  or  is  it  sufficient  that  the  toxins 
should  be  carried  by  the  blood  and  lymph  from  some  other 
seat  of  manufacture  ?  It  does  not  seem  possible  to  give  an 
absolute  answer  to  this  question,  though  the  presence  of 
bacteria  in  the  brains  of  the  three  cases  we  have  examined 
suggests  that  its  affection  depends  on  the  direct  invasion  of  it 
by  the  bacteria.  The  occurrence  of  hemichorea  also  makes  a 
local  infection  probable,  as  unilateral  sj'mptoms  can  be  scarcely 
attributed  to  a  general  infection  ;  it  is  also  supported  by  the 
previous  demonstration  of  the  diplococcus  rheumaticus  in  all 
the  other  important  lesions  it  produces.  On  the  other  hand, 
it  must  be  borne  in  mind  that  it  has  been  shown  by  Laignel- 
Lavastine  that  similar  changes  in  the  brain  ceUs  may  be  the 
result  of  tuberculous  toxaemia  without  bacterial  infection  of 
the  brain,  and  Babes  and  others  have  found  similar  cell  changes 
after  the  experimental  injection  of  toxins  alone.  The  examina- 
tion of  a  series  of  brains  from  cases  of  acute  rheumatism 
without  cerebral  symptoms  will  be  necessary  to  decide  this 
point. 


256  A  CONTRIBUTION  TO  THE 

It  now  remains  to  attempt  an  explanation  of  the  production 
of  chorea  by  these  toxins,  whether  produced  locally  or  cir- 
culating in  the  blood  and  lymph.  Here  we  have  to  deal  with 
the  little-understood  physiology  of  the  nerve  cell  and  our 
arguments  are  consequently  more  or  less  limited  to  analogy. 
Thus,  it  is  well  known  that  symptoms  of  instability  and  over- 
action  of  the  nerve  cells,  analogous,  if  not  similar,  to  those  of 
chorea,  may  result  from  the  action  of  the  toxin  of  tetanus  and 
that  similar  excess  of  movement  is  produced  by  strychnine. 
Nor  does  the  possible  analogy  end  here.  The  excess  of  activity 
produced  by  strychnine,  and  perhaps,  too,  by  tetanus,  may  be 
followed  by  paralysis  of  the  concerned  movements,  presumably 
due  to  exhaustion  of  the  nervous  centres,  and  it  is  possible  that 
some  of  the  choreal  palsy  may  be  due  to  a  similar  exhaustion 
of  the  active  centres,  although  it  seems  to  us  more  probable 
that  the  palsy  of  movement  so  frequently  seen  in  chorea  is  a 
direct  effect  of  toxic  action.  It  is  conceivable  that  the  same 
toxin  which  produces  symptoms  of  excitation  may,  when 
acting  in  greater  concentration  or  more  rapidly,  paralyse  the 
functions  of  the  cells.  Such  a  reversal  of  action  is  seen  on  the 
administration  of  morphine  or  chloroform  ;  small  doses  acting 
for  a  short  time  produce  excitation,  while  in  larger  amount 
they  annul  the  functions  of  the  previously  excited  centres. 
This  toxin,  though  probably  specific  in  the  sense  that  it  is 
constantly  the  product  of  a  single  variety  of  bacteria,  has 
certainly  no  special  action  on  any  part  of  the  central  nervous 
system  in  the  sense  that  it  affects  these  and  spares  the  others, 
for  both  the  vascular  and  nerve  cell  changes  were  found  in 
every  region  of  the  brain  and  brain-stem.  The  explanation  of 
the  predominant  affection  of  the  motor  system  in  chorea  is 
probably  that  its  symptoms  are  always  the  most  apparent  and 
that  it  is  the  system  which  reacts  most  easily  to  excitation. 
But  chorea  is  not  composed  of  one  symptom  alone,  there  may 
be  in  addition  positive  or  negative  symptoms  of  speech, 
sensation,  and  even  of  the  highest  psychical  state.  The 
anatomical  basis  of  such  disturbances  of  function  is  repre- 
sented by  the  changes  described  in  the  nerve  cells  in  the 
different  parts  of  the  brain. 

The  aim  of  this  paper  is  such  that  it  is  not  necessary  to 
commit  ourselves  to  a  definite  expression  of  opinion  as  to  the 
disturbance  of  what  portion  of  the  nervous  system  yields  the 


PATHOLOGY  OF  CHOREA  257 

predominant  symptom  of  chorea.  It  has  been  assumed, 
though  often  only  tacitly,  by  the  majority  of  authors  that 
the  higher  motor  centres  are  concerned  and  it  has  therefore 
been  placed  in  the  cerebral  cortex,  or,  in  the  prelocalisation 
days,  in  the  corpus  striatum.  As  Dr.  Hughlings  Jackson  has 
so  clearly  shown,  the  nature  and  distribution  of  the  move- 
ments, as  well  as  the  general  physiology  of  the  disease,  confirm 
this  view,  but  the  pathological  changes  are  so  general  and  wide- 
spread throughout  the  whole  central  nervous  system  that  they 
can  neither  support  nor  contradict  any  theory  of  localisation. 

II.  Chorea  and  Rheumatism.  We  are  thus  led  by  this 
study  to  the  conclusion  that  the  causation  of  chorea  is  to  be 
found  in  the  action  of  bacterial  poisons  on  the  brain.  Further, 
the  available  evidence  points  to  the  occurrence  of  a  local 
infection  to  which  the  widespread  changes  in  the  nervous 
system  are  due.  Finally,  we  believe  that  this  infection  is  of  a 
rheumatic  nature  ;  it  is,  then,  necessary  to  see  how  far  it  is 
possible  to  correlate  this  conclusion  with  the  association  of 
chorea  and  rheumatism. 

The  first  point  in  this  consideration  is  the  frequency  of  the 
association  of  chorea  and  rheumatic  fever.  This  is  explained 
by  looking  upon  chorea  in  the  rheumatic  as  a  symptom  of 
rheumatic  infection  and  by  regarding  the  "  diplococcus  rheu- 
maticus  "  as  the  cause.  •  This,  too,  explains  the  clinical  truth 
that  chorea  may  be  the  first  evidence  of  acute  rheumatism  or 
be  one  of  many  coincident  manifestations  or  be  a  late  episode 
of  the  disease.  Which  of  these  events  may  happen  will  depend 
upon  the  date  at  which  the  cerebral  infection  occurs.  If  we 
accept  the  undoubted  fact  that  chorea  may  be  the  first  symptom 
of  acute  rheumatism  we  are  at  once  confronted  with  the 
question  whether  or  not  chorea  is  only  a  manifestation  of  acute 
rheumatism.  It  will  be  a  distinct  advance  in  our  knowledge 
when  the  answer  to  this  is  finally  settled.  The  difficulty  is 
apparent  and  turns  upon  the  doubt  as  to  whether  such  move- 
ments and  such  cerebral  disturbance  as  we  see  in  chorea  can 
be  produced  by  more  than  one  agent.  At  the  present  time 
there  is  evidence  upon  both  sides  but  the  bulk  of  it  strongly 
favours  the  view  that  chorea  is  mostly  rheumatic  and  that 
when  chorea  occurs  without  any  history  of  rheumatism  it  is 
presumably  the  primary  rheumatic  symptom  and  in  practical 
medicine  is  best  looked  upon  as  a  stamp  of  rheumatism. 

17 


258  A  CONTRIBUTION  TO  THE 

The  tendency  for  chorea  to  relapse  or  to  occur  several 
times  in  the  life  of  an  individual  is  explained  in  precisely  the 
same  way  as  the  relapses  and  recurrences  of  rheumatic  heart 
disease  and  arthritis  ;  that  is  to  say,  either  there  is  a  fresh 
outburst  of  a  slumbering  infection  or  a  fresh  infection  has 
occurred.  The  onset  of  chorea  is  not  unlike  the  onset  of  the 
other  rheumatic  manifestations,  for,  as  with  these,  it  may  be 
gradual,  subacute  or  acute.  If  the  infection  is  slow  in  making 
itself  felt,  and  yet  eventually  succeeds,  then  the  course  of  the 
chorea  is  slow.  The  acute  cases,  on  the  other  hand,  recover 
more  rapidly.  Should  chorea  arise  while  the  patient  is  under 
observation  this  sequence  of  events  is  observed  whatever 
method  of  treatment  is  adopted,  the  stage  of  onset,  the  stage 
of  the  developed  disease,  and,  lastly,  the  stage  of  retrogression. 
This  is  the  course  that  we  notice  in  all  infections  that  cannot 
be  cut  short  by  some  specific  remedy. 

When  chorea  follows  acute  arthritic  or  cardiac  rheumatism 
the  cerebral  infection  may  date  from  the  original  one,  and 
have  remained  latent  for  some  time,  for  there  is  no  doubt  that 
chorea  may  smoulder  on  for  weeks  without  distinctly  declaring 
itself.  In  other  cases  an  entirely  new  infection  may  have 
occurred,  which  this  time  has  attacked  the  brain.  Lastly,  the 
cerebral  infection  may  be  metastatic,  in  the  sense  that  it  has 
arisen  after  the  original  attack  of  acute  rheumatism  by  a 
metastasis  from  a  focus  of  infection  elsewhere,  which  itself  was 
the  result  of  the  original  attack  ;  this  focus  may  be  situated, 
for  instance,  in  the  heart  or  in  the  joints.  As  Vernon  Shaw 
has  demonstrated  in  animals,  a  primary  focus  in  a  joint, 
produced  by  a  local  injection  of  the  diplococcus,  may  be 
followed  by  the  appearance  of  pericarditis.  Chorea  is  thus 
very  reasonably  explained  both  as  the  first  symptom  and  the 
last  of  acute  rheumatism,  and  when  it  occurs  simultaneously 
with  arthritis  and  endocarditis  it  is  clearly  part  of  a  widespread 
infection.  The  complete  recovery  that  so  frequently  occurs  in 
chorea  is  not  infrequently  brought  forward  as  an  argument 
against  its  rheumatic  origin.  It  is,  however,  clear  that  acute 
rheumatism  is  a  disease  to  which  there  is  great  resistance,  for 
it  is  rarely  fatal  ;  and  it  is  also  evident  that  the  various  tissues 
resist  the  poisons  with  different  degrees  of  success.  The  heart 
often  recovers  partially  but  is  usually  maimed  ;  the  joints 
often  recover  completely,  pleurisy  generally  leaves  adhesions, 


PATHOLOGY  OF  CHOREA  259 

but  the  subcutaneous  nodules  and  cutaneous  eruptions  dis- 
appear. The  renal  inflammation,  again,  is  usually  transitory. 
Chorea  is  to  be  grouped  among  the  more  transitory  of  the 
rheumatic  lesions,  for  although  there  is  no  doubt  that  some 
cases  may  last  for  many  years  the  anatomical  lesions  are 
clearly  recoverable  as  shown  from  the  pathological  changes  in 
these  cases. 

At  this  point  we  would  make  passing  allusions  to  the 
probability  that  even  more  delicate  changes  occur  in  the 
nervous  system  as  the  result  of  rheumatism.  Clinical  observers 
have  pointed  out  that  rheumatic  children  are  singularly 
nervous  and  emotional  and  there  is  no  doubt  that  a  child's 
nature  may  be  greatly  changed  by  an  attack  of  rheumatism, 
particularly  if  this  should  be  of  the  cerebral  type.  To  our 
knowledge  parents  have  volunteered  this  statement  where 
examination  has  shown  that  no  cardiac  lesion  has  been  left 
behind  and  the  attack  of  rheumatism  has  certainly  subsided. 
It  is  possible  that  such  psychical  alterations  are  the  result  of 
organic  changes  of  an  even  more  delicate  nature  than  those 
met  with  in  chorea. 

A  difficulty  which  attends  the  complete  explanation  of 
other  infective  processes  which  affect  the  brain  is  equally 
present  with  chorea.  We  cannot  say  why  in  some  cases  the 
brain  suffers  and  in  others  it  does  not.  The  well-known 
importance  attached  to  fright  in  the  aetiology  of  chorea  has 
close  bearing  upon  this  difficulty,  for  overstrain  of  any  system 
tends  to  lower  its  vitality  and  in  the  case  of  the  nervous  centres, 
whether  that  overstrain  be  abrupt,  as  in  fright,  or  chronic,  as 
in  the  strain  of  school-work  or  mental  anxiety,  the  lowering  of 
the  vitality  is  a  predisposing  cause  for  the  rheumatic  infection 
to  gain  a  foothold. 

Part  IV. — Chorea  and  Pregnancy 

The  third  case  in  which  chorea  was  associated  with  pregnancy 
raises1  two  questions  of  importance.  Firstly,  whether  this 
chorea  is  a  rheumatic  chorea  intensified  by  the  condition,  and 
secondly,  a  far  wider  one  concerned  with  the  influence  of 
pregnancy  and  the  puerperal  state  upon  the  rheumatic  infec- 
tion. Chorea  in  pregnancy  is  probably  a  rheumatic  chorea. 
We  get  support  for  this  statement  from  the  clinical  observations 


26o  A  CONTRIBUTION  TO  THE 

of  others  upon  the  association  of  rheumatism  and  chorea  in 

pregnancy.     Thus  in  a   recent   paper   by   Wall  and    Russell 

Andrews  6  Buist's  statistics  are  quoted,  who  found  that  in 

226  cases  of  chorea  in  pregnancy  45  gave  a  previous  history 

of  rheumatism  and  66  a  previous  history  of  chorea.     From 

their  own  observations  they  found  that  in  23  out  of  37  cases 

of  chorea  in  pregnancy  there  was  a  previous  history  of  chorea 

and  in  16  out  of  37  a  previous  history  of  rheumatism.     Still 

more   recent   and   equally   convincing   evidence   is   furnished 

in  a  paper  by  Dr.  Herbert  S.  French  and  Mr.  H.  T.  Hicks.7 

Here  29  consecutive  cases  of  chorea  gravidarum  were  reviewed 

from  the  records  of  Guy's  Hospital  and  in  no  fewer  than  19 

of  these  there  was  a  previous  history  of  rheumatism  or  chorea 

and  15  of  these  19  had  suffered  from  chorea  before  marriage. 

As  a  result  of  their  investigations  these  authors  add  :    "  This 

is  so  large  a  proportion  of  the  whole  that  we  feel  convinced 

that  chorea  gravidarum  and  infantile  chorea  have  a  similar 

pathology."     This  single  case  of  ours  strengthens  the  position 

to  this  extent,  that  it  has  enabled  us  to  show  the  presence  of  a 

diplococcus  in  the  nervous  system  and  heart  valves  and  to 

demonstrate  that  the  morbid  changes  in  the  brain  are  essentially 

similar  to  those  in  rheumatic  chorea.     Further,  the  mother  of 

the  patient  was  at  the  same  time  in  Guy's  Hospital  suffering 

from  recurrent  ascites  due  to  heart  disease.     There  are,  then, 

the  chorea,  the  condition  of  endocarditis  of  the  mitral  valve 

described  above,  and  the  nature  of  the  mother's  illness,  which 

legitimately  suggest  that  this  woman  was  suffering  from  a 

rheumatic  chorea.     It  will  not  be  forgotten  that  in  childhood 

chorea  may  be  the  only  evidence  of  rheumatism,  and  it  is 

difficult  not  to  believe  that  when  in  a  case  of  chorea  we  search 

for  a  history  of  rheumatism  we  may  often  be  in  the  position  of 

one  searching  for  a  history  of  tuberculosis  in  a  patient  suffering 

from   tubercular   meningitis.     We    are,   in   fact,   looking   for 

evidence  of  a  disease  with  that  evidence  staring  us  in  the  face. 

It   is   also    becoming   increasingly    apparent    that    the    most 

frequent  cause  of  chorea  in  pregnancy  is,  in  all  probability,  a 

rheumatic  infection.     Two  cases  under  the  care  of  one  of  us 

are  worth  mention  in  this  context.     One  of  these  while  a 

child  was  a  patient  in  the  Hospital  for  Sick  Children,  Great 

Ormond-?treet,  with  chorea  and  rheumatic  endocarditis.     At 

the  age  of  16  years  she  became  pregnant  and  was  admitted 


PATHOLOGY  OF  CHOREA  261 

to  University  College  Hospital  suffering  from  chorea  of  terrible 
severity  from  which,  after  a  very  long  and  severe  illness,  she 
recovered.  The  other  was  a  young  woman  who  suffered  from 
rheumatism  with  chorea  as  a  girl,  who  passed  through  a  first 
pregnancy  without  chorea  and  developed  chorea  12  months 
later  when  she  was  not  pregnant.  Finally,  it  is  recognised 
that  induction  of  labour  does  not  so  influence  the  course  of 
these  cases  of  chorea  that  the  pregnancy  can  be  claimed  to  be 
more  than  a  predisposing  cause.  All  these  points  suggest  that 
the  chorea  in  pregnancy  is  of  the  same  nature  as  the  chorea  of 
childhood. 

The  second  and  wider  question  of  the  influence  of  pregnancy 
and  the  puerperal  state  upon  rheumatic  infection  needs  pro- 
longed investigation.  We  have,  on  the  one  hand,  a  great 
infective  process,  the  rheumatic,  and  on  the  other,  an  important 
physiological  process,  which  in  some  measure  disturbs  the 
entire  metabolism  of  the  individual.  Chorea  is  more  obstinate 
and  dangerous  in  pregnancy,  heart  disease  is  liable  to  be  more 
active,  and  arthritis  more  obstinate.  Concerned  with  the  same 
problem  is  the  possibility  that  a  puerperal  fever  may  result 
from  a  rheumatic  infection  at  the  end  of  pregnancy  and  it  is 
known  that  direct  infection  of  the  fcetus  may  occur. 

Finally,  we  would  point  out  that  the  conclusions  from  our 
paper  in  the  first  place  support  the  clinical  evidence  that 
chorea  is  a  manifestation  of  acute  rheumatism  ;  and  secondly, 
that  the  demonstration  of  diplococci  in  each  of  the  three  cases 
is  a  striking  confirmation  of  the  assertion  that  "  the  diplococcus 
rheumaticus  "  is  the  infective  agent  in  acute  rheumatism. 

REFERENCES 

1  Practitioner ,  August  1906. 

2  Edinburgh  Medical  Journal,  vol.  xiv,  1868. 

3  Medical  Times  and  Gazette,  1875. 

4  Ibid.  1869.  5  Ibid.  1875. 
*      6  Transactions  of  the  Medical  Society,  vol.  xxvi. 

7  Practitioner,  August  1906. 


PAPER  NO.  XX 

SOME    FURTHER    INVESTIGATIONS   AND 

OBSERVATIONS  UPON  THE  PATHOLOGY 

OF  RHEUMATIC  FEVER 

(Reprinted  from  the  Lancet,  June  4,  19 10) 

Further  criticisms  of  our  previous  communications  are  dealt  with 
in  the  first  fart  of  this  paper,  and  answered  so  far  as  lay  in  our  power 
by  counter-statements  and  further  investigations.  Indirect  support  of 
the  earlier  papers  was  now  forthcoming  in  the  researches  of  Aschojf, 
Tawara,  and  Carey  Coombs  upon  the  myocardium  in  rheumatism. 
Reference  to  our  second  paper  in  this  book  will  show  that  these  authors 
had  elaborated  the  cardinal  facts  recorded  there,  and  in  so  doing  had 
corroborated  the  accuracy  of  the  observations.  Through  the  kindness 
of  Dr.  Lauriston  Shaw  and  Dr.  A .  F.  Hertz  we  were  able  to  investigate 
a  case  of  rheumatic  hyperpyrexia,  and  the  result  of  this  research  is 
given. 

A  further  step  in  the  study  of  the  tonsils  suggested  by  Mr.  George 
Waugh  is  described,  and  the  production  of  chronic  forms  of  arthritis 
by  means  of  the  diplococcus  recorded. 

It  is  now  close  upon  ten  years  since  we  published  in  the 
Lancet x  the  first  evidence  that  we  had  at  our  disposal  upon 
the  pathology  of  acute  rheumatism,  and  while  bringing  forward 
some  additional  points  we  would  shortly  review  the  position 
as  it  seems  to  us  to  stand  to-day. 

In  our  first  paper  we  attempted  to  show  the  relation  of  our 
own  investigations  to  those  of  others,  and  with  this  we  need 
not  deal  again  here  ;  in  our  later  papers  we  also  referred  to 
the  researches  of  other  workers  upon  this  subject,  notably  Dr. 
E.  W.  Ainley  Walker,2  Dr.  W.  Vernon  Shaw,3  and  Professor 
J.  M.  Beattie.4  Much  interesting  criticism  has  been  directed 
against  the  two  main  conclusions  we  have  so  often  stated, 
and  which  we  venture  to  repeat  here  :  first,  that  a  diplococcus, 
streptococcus,  or  micrococcus  is  a  cause  and  most  probably 

262 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     263 

the  only  exciting  cause  of  acute  rheumatism  ;  secondly,  that 
acute  rheumatism  may  be  a  cause  of  simple  and  malignant 
endocarditis.  We  will  at  once  clear  the  ground  by  adding  that 
we  are  as  convinced  now  as  we  were  before  that  both  these 
conclusions  hold  good.  Some  of  the  criticisms  that  have  been 
put  forward  have  been  already  answered,  and  in  this  paper  we 
shall  attempt  to  deal  further  with  one  of  the  most  recent  of  them. 

It  has  been  suggested  that  we  have  been  describing  an 
agonal  or  terminal  infection,  but  we  have  brought  forward 
conclusive  evidence  to  show  that  some  of  the  patients  from 
whom  the  micrococcus  was  isolated  lived  for  many  weeks 
afterwards,  and  that  others  were  alive  and  at  work  some 
years  later.  This  criticism  may  then  be  dismissed  once  and 
for  all.  Again,  it  has  been  suggested  that  the  micrococcus 
may  be  present  in  complicated  rheumatism  as  an  epipheno- 
menon,  as  a  cause,  that  is,  of  the  complications.  Having 
produced  experimentally  the  important  lesions  of  the  disease,5 
we  naturally  ask  in  return  what  is  to  constitute  acute  rheu- 
matism when  deprived  of  arthritis,  carditis,  nodules,  choreiform 
movements,  and  pleurisy  ?  We  hold  that  there  is,  as  in 
tuberculosis,  only  a  predisposition  left  in  the  sense  that  there 
is  some  vulnerability  of  the  tissues  to  this  infection,  and  that 
there  is  no  mysterious  disease  "  rheumatism,"  which  is  always 
associated  with  secondary  infections.  The  idea  that  rheu- 
matism produces  arthritis,  but  that  a  secondary  infection 
produces  the  endocarditis  which  is  so  often  associated,  may 
now  be  looked  upon  as  contrary  to  all  accurate  knowledge. 
Another  difficulty  has  been  raised  that  this  micrococcus  is  not 
constantly  present  and  that  we  have  even  ourselves  not  always 
succeeded  in  isolating  it.  This  is  naturally  a  troublesome 
question  to  answer,  and  it  has  been  added,  that  when,  on  the 
one  hand,  some  observers  are  repeatedly  finding  this  micro- 
coccus, and  others  of  equal  reputation  are  always  failing,  the 
success  of  those  who  obtain  positive  results  is  somewhat 
suspicious. 

If,  then,  we  fail  to  find  the  infective  agent  we  must  be 
convicted  out  of  our  own  mouths,  and  if  we  find  it  we  are 
suspects  because  others  do  not  succeed. 

With  regard  to  this  micro-organism,  all  our  own  investi- 
gations go  to  prove  that  it  is  very  constant.  We  have  not 
demonstrated  it  in  every  case  of  acute  rheumatism,  but  that  is  no 


264  FURTHER  INVESTIGATIONS  UPON 

proof  that  it  may  not  be  present,  and,  on  the  other  hand,  we 
have  succeeded  so  repeatedly  that  we  believe  that  we  are  in 
the  position  to  say  that  if  in  any  case  one  had  unlimited  scope 
and  time  for  investigations  the  results  would  be  quite  constant. 
It  is  abundantly  clear  that  we  must  choose  the  cases  with  care, 
and  with  a  knowledge  of  pathological  processes,  selecting  those 
in  which  the  disease  is  active.  It  is  a  hopeless  undertaking  to 
investigate  a  case  of  chronic  rheumatic  heart  disease  which 
has  been  in  extremis  from  secondary  cardiac  failure  of 
mechanical  origin,  the  result  of  the  scars  of  former  disease. 
Again,  from  one's  knowledge  of  rheumatism,  it  is  hardly 
likely  that  10  cubic  centimetres  of  blood  taken  at  random 
from  the  general  circulation  is  going  to  yield  a  positive  result 
in  a  mild  rheumatic  arthritis. 

The  particular  points  that  we  wish  to  lay  stress  on  now 
with  reference  to  the  isolation  of  this  micrococcus  are  that 
we  have  upon  several  occasions  demonstrated  it  in  fatal 
rheumatism  when  it  has  been  simultaneously  found  by  others 
in  the  same  case  ;  secondly,  that  we  have  worked  with  it 
when  isolated  not  by  ourselves  but  by  others  ;  and  lastly,  that 
we  have  isolated  it  from  pericardial  fluids  obtained  from  fatal 
pericarditis  by  others  who  have  forwarded  to  us  the  fluids  in 
sealed  tubes.  These  tubes  we  have  incubated  without  opening, 
and  as  was  the  case  in  the  first  result  we  ever  reported,  the 
diplococcus  was  found  in  these  fluids  after  incubation — that  is, 
growing  in  the  natural  medium. 

Example  No.  I.  A  girl,  aged  7  years,  was  admitted  to 
University  College  Hospital  on  March  25,  1906,  with  a  three 
weeks'  history  of  acute  malaise,  vomiting,  and  multiple 
arthritis.  Chorea  and  severe  pericarditis  developed  with  endo- 
carditis, and  death  occurred  after  barely  four  weeks'  illness. 
There  had  been  a  previous  attack  of  rheumatic  fever  at  five  years 
of  age.  The  post-mortem  investigation  showed  pericarditis 
of  the  usual  rheumatic  type. 

Dr.  F.  H.  Thiele,  clinical  pathologist  to  University  College 
Hospital,  obtained  a  pure  growth  of  a  diplococcus  from  the 
heart's  blood.  Dr.  T.  Lewis  demonstrated  a  diplococcus  in  the 
pericardial  fluid.  We  also  found  it  in  the  exudation,  and  in  the 
laboratory  it  conformed  to  the  characters  of  the  diplococcus 
rheumaticus,  and  on  experiment  produced  multiple  arthritis 
and  pericarditis  of  the  usual  type. 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     265 

Example  No.  2,  In  June  1908,  Dr.  J.  Graham  Forbes, 
bacteriologist  to  the  Hospital  for  Sick  Children,  Great  Ormond 
Street,  isolated  a  diplo-streptococcus  during  life  from  the  blood 
of  a  child  in  the  hospital  suffering  from  carditis,  chorea,  and 
nodules.  This  diplo-streptococcus  had  the  usual  appearances 
and  growth  on  culture.  Dr.  Forbes  kindly  sent  us  a  sub- 
culture and  with  it  we  repeated  an  experiment  we  have  under- 
taken before — the  subcutaneous  inoculation  of  a  large  dose  of 
the  culture.  No  suppuration  resulted  and  in  a  short  time  all 
signs  of  an  inflammatory-  reaction  had  disappeared  as  in  our 
previous  experience. 

It  is  interesting  that  the  subcultures  from  this  case  growing 
on  unsuitable  media  showed  a  transition  of  the  diplococcus 
into  bacillary  forms.  Those  who  have  followed  the  researches 
upon  Achalme's  bacillus  will  remember  that  in  the  last 
few  years  it  had  been  observed  this  bacillus  may  assume  a 
diplococcal  form. 

Example  No.  3.  Dr.  A.  Salisbury  Macnalty,  resident  medical 
officer  at  the  Brompton  Hospital  for  Diseases  of  the  Chest,  in 
April  1909  kindly  sent  us  a  culture  of  a  diplococcus  which  he 
had  isolated  post-mortem  from  a  case  of  rheumatic  pericarditis. 
This  micro-organism  showed  the  usual  characters  of  the 
diplococcus  rheumaticus  and  produced  a  transitory  arthritis  of 
the  right  knee-joint  on  intravenous  inoculation  into  a  rabbit. 

Example  No.  4.  In  August  1909,  through  the  kindness  of 
Dr.  Lauriston  Shaw  and  Dr.  A.  F.  Hertz  from  Guy's  Hospital, 
pericardial  and  cerebro-spinal  fluid  were  taken  from  a  case  of 
fatal  rheumatic  hyperp3*rexia  and  were  forwarded  to  us  in 
sterilised  sealed  tubes  ;  the  results  are  fully  detailed  later  in 
this  paper. 

We  believe  that  these  examples  will  dispose  of  any  suspicion 
that  our  success  in  isolation  of  the  diplococcus  is  dependent 
upon  some  mysterious  chance,  and  we  need  only  recall  the 
work  of  Ainley  Walker,  Vernon  Shaw,  and  Beattie  in  this 
country  to  make  it  clear  that  the  diplococcus  is  an  entit\T. 

With  regard  to  the  specificity  of  this  micro-organism  we 
would  again  repeat  that  in  our  experience  no  other  can  be 
found  in  the  rheumatic  lesions  in  man  which  will  produce 
similar  lesions  in  animals.  Undoubtedly  various  micrococci 
may,  for  example,  produce  experimental  endocarditis,  as 
they   may   also   produce   endocarditis   in  man,    but    various 


266  FURTHER  INVESTIGATIONS  UPON 

micrococci  are  not  found  in  human  rheumatic  endocarditis  which 
will  reproduce  the  disease.  Again,  various  infections  may 
cause  experimental  pericarditis,  but  only  one  in  our  experience 
can  produce  rheumatic  pericarditis  in  man  and  also  experi- 
mental pericarditis.  We  hold,  too,  that  Triboulet,  Wasser- 
mann,  Walker,  Vernon  Shaw,  Beattie,  and  ourselves  have 
shown  that  the  general  characteristics  of  this  streptococcus  are 
as  well  differentiated  as  those  of  other  members  of  this  group. 
It  would,  nevertheless,  be  wrong  to  ignore  the  recent  investiga- 
tions by  Rosenthal  and  others  in  France  upon  Achalme's 
bacillus,  or  to  hide  the  fact  that  they  claim  that  they  have 
proved  its  causal  relation  to  the  disease.  We  can  only  repeat 
that  we  have  failed  to  demonstrate  this  bacillus,  and  would 
add  that  even  the  French  observers  lay  stress  upon  its  pleo- 
morphism  and  its  occurrence  in  diflococcic  form.  Thus 
Rosenthal 6  mentions  the  reception  of  a  diplococcus  from 
Belgium  which  had  been  isolated  from  the  blood  of  a  case  of 
active  rheumatism.  This,  when  transferred  to  his  anaerobic 
media,  developed  into  the  bacillus  of  Achalme,  but  in  aerobic 
culture  it  retained  its  diplococcal  form.  Rosenthal  and  others 
each  year  that  passes  are  apparently  striving  to  prove  that 
this  diplococcus  is  the  bacillus  of  Achame  growing  in  unsuit- 
able media.  We,  on  the  other  hand,  maintain  that  the 
diplococcus  grows  naturally  in  aerobic  media,  but  may, 
as  we  stated  eight  years  ago,  when  growing  in  unsuitable 
media,  assume  bacillary  forms.  Whether  these  bacillary  forms 
are  Achalme's  bacillus  we  cannot  say. 

In  this  country  we  believe  the  tendency  has  been  to  mystify 
the  main  question — the  aetiology  of  rheumatism — by  intro- 
ducing a  classification  of  the  streptococci  by  certain  sugar 
ferment  tests  in  the  laboratory.  Apparently,  as  an  outcome 
of  this,  we  have  to  be  satisfied  with  the  description  of  a  strepto- 
coccus salivarius  or  faecalis.  That  a  streptococcus  in  the  saliva 
or  fasces  should  give  certain  tests  in  the  laboratory  is  not  likely 
to  be  of  any  practical  moment  unless  some  peculiar  strepto- 
cocci develop  de  novo  in  these  situations.  Seeing  that  the 
nature  of  this  group  of  micro-organisms  is  much  altered  by 
the  media  in  which  they  grow,  such  a  classification  is  in  our 
present  state  of  knowledge  most  perplexing.  Instance,  for 
example,  the  diplococcus  of  rheumatism  :  it  undoubtedly 
locates  itself  in  the  tonsils,  but  are  not  these  washed  by  the 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     267 

saliva,  and  is  not  the  saliva  swallowed  into  the  stomach  and 
passed  into  the  intestines  with  the  food  ?  Which  is  of  the 
greater  importance — that  a  diplococcus  can  be  isolated  from  a 
rheumatic  angina  and  reproduce  rheumatic  lesions,  or  that  a 
diplococcus  isolated  from  the  saliva  and  faeces  can  give  some 
apparently  specific  sugar  tests  in  a  laboratory  ?  Lastly,  what 
alterations  in  character  and  virulence  might  not  the  diplococcus 
undergo  when,  dislodged  from  the  tonsils  by  the  saliva,  it 
lingers  in  a  new  environment  such  as  the  faeces  ? 

Is  it  not  an  outcome  of  the  confusion  which  arises  from 
such  a  classification  that  in  a  valuable  paper  on  infective 
endocarditis  we  read  as  follows  :  "It  would  obviously  be 
fallacious  to  conclude  that  any  micro-organism  isolated  from 
the  blood  of  a  patient  with  fever,  endocarditis,  and  chorea  had 
any  necessary  connection  with  the  cause  of  rheumatic  fever  ' '  ? 
Seeing  that  a  streptococcus  isolated  from  acute  rheumatic 
lesions,  and  let  us  add  also  from  the  blood  in  acute  rheumatism, 
can  produce  endocarditis,  fever,  and  choreiform  movements, 
as  more  than  one  skilled  bacteriologist  has  shown,  it  is  difficult 
to  see  how  the  conclusion  that  this  streptococcus  has  some 
necessary  connection  with  rheumatic  fever  can  obviously  be 
fallacious.  It  may  be  a  wrong  conclusion  but  it  seems  a 
reasonable  one. 

Indirect  Support  from  Recent  Investigations 

We  would  next  point  out  that  in  the  last  ten  years  the 
trend  of  scientific  investigation  and  clinical  observation  has 
strengthened  our  position  in  spite  of  the  fact  that  some  of 
these  observations  have  been  made  by  those  who  have  not 
had  the  causation  of  rheumatism  in  view,  and  others  have 
been  made  by  those  who  have  not  accepted  our  explanation 
and  yet  have  been  of  assistance  in  bringing  us  support  by 
their  independent  observations. 

To  take  the  first  type  of  evidence,  we  would  allude  to  a 
paper  written  by  one  of  us  in  1898  and  read  at  the  Royal 
Medical  and  Chirurgical  Society  (Paper  No.  2).7  In  this  contri- 
bution it  was  demonstrated  that  in  rheumatic  carditis  scattered 
foci  of  inflammatory  change  were  to  be  found  in  the  connective- 
tissue  framework  of  the  heart  springing  from  the  region  of 
the  small  blood-vessels.  It  was  further  shown  that  in  these 
regions  gross  changes  might  be  found  in  the  neighbouring 


268  FURTHER  INVESTIGATIONS  UPON 

muscular  fibres.  This  distribution,  it  was  pointed  out,  strongly 
favoured  the  view  that  they  were  a  result  of  some  bacterial 
infection.  Later,  when  we  identified  the  infection,  we  pro- 
duced and  showed  at  the  Pathological  Society  of  London 
experimental  carditis  of  the  same  order.8  These  observations 
have  been  expanded,  notably  by  Aschoff  and  Tawara  9  and 
Carey-Coombs,10  who  have  maintained  that  they  are  specific 
lesions,  and  their  importance  has  been  insisted  upon  from  an 
entirely  different  standpoint  to  ours.  We  emphasised  their 
importance  as  a  factor  in  the  heart  failure  of  rheumatic  morbus 
cordis.  Others,  led  by  Dr.  James  Mackenzie,  have  dwelt  upon 
their  importance  in  connection  with  cardiac  arrhythmias  and 
the  primitive  cardiac  muscle.  If  we  recall  that  Keith,  in  one 
of  his  latest  papers  which  he  read  upon  the  anatomical  side  of 
this  question  before  the  Medical  Society  of  London  in  1909, 
stated  his  conviction  that  cardiac  nerve  and  cardiac  muscle 
come  into  such  close  relation  that  they  may  fairly  be  said  to 
merge  in  the  primitive  muscular  fibre  of  the  cardiac  tube,  it 
becomes  at  once  apparent  that  these  focal  lesions  of  rheumatic 
carditis  must  have  an  important  bearing  upon  this  aspect  of 
cardiac  disease. 

Since  Aschoff  published  his  observations  they  have  attracted 
considerable  attention  in  this  country  not  because  of  their 
bearing  upon  the  aetiology  of  rheumatism,  but  because  they  are 
concerned  with  the  ever  fascinating  problem  of  the  heart-beat. 

Next  we  will  take  the  second  type  of  evidence  supplied  by 
others  who  are  opposed  to  our  explanations,  but  who  in  spite 
of  this  have  given  us  indirect  support. 

To  us  there  are  few  more  curious  points  in  the  history  of 
cardiac  pathology  than  the  attitude  held  by  many  toward 
rheumatic  endocarditis.  They  admit  it  is  infective ;  the 
evidence,  indeed,  in  its  favour  is  overwhelming,  but  they 
hesitate  to  admit  that  this  endocarditis  may  become  malignant. 
When,  however,  we  analyse  the  meaning  of  this  malignancy  as 
applied  to  endocarditis,  we  find  it  expresses  an  inability  on 
the  part  of  the  damaged  tissues  to  overcome  the  local  infection. 
There  may  be  partial,  and  exceptionally  even  complete,  success, 
but  the  rule  is  failure.  This  malignancy  is,  then,  no  new 
mysterious  change  in  the  tissues,  and  as  its  antecedent  we  find 
the  most  frequent  is  previous  rheumatic  endocarditis. 

Now  come  the  curious  conclusions  we  are  asked  to  accept  : 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     269 

firstly,  that  an  infection  in  the  endocardium  of  rheumatic 
origin  is  always  simple — that  is,,  is  always  capable  of  healing  ; 
and,  secondly,  that  malignant  endocarditis  after  rheumatism 
is  always  caused  by  a  secondary  infection  of  valves  scarred  by 
previous  disease. 

The  first  conclusion  is  strange,  because  infections  of  the 
rheumatic  type  are  not  likely  to  be  always  "  simple  "  ;  they 
clearly  vary  in  virulence  as  do  all  other  infections  of  the  same 
group.  The  second  conclusion  that  bacteria  prefer  scarred 
valves  is,  in  our  opinion,  a  false  one.  There  is  no  evidence 
that  bacteria  prefer  scar  tissue  ;  in  fact,  all  evidence  is  against 
it.  If  the  so-called  scarred  valves  of  rheumatism  are  examined 
it  will  be  found  that  the  vegetations  are  not  really  scar  tissue, 
but  are  masses  of  unhealthy  necrotic  material  which  the  scar 
formation  has  not  invaded.  We  hold  that  in  this  necrotic 
tissue  the  rheumatic  infection  that  caused  the  original  endo- 
carditis often  lurks  quiescent  but  not  destroyed.  The  forma- 
tion of  scar  tissue  makes  it  difficult  for  leucocytosis  to  deal 
with  bacteria  in  these  isolated  necrotic  patches,  which,  border- 
ing as  they  do  on  the  general  circulation,  are  as  much  a  source 
of  danger, as  a  necrotic  gland  close  to  the  circulation  is  in 
tuberculosis. 

The  recent  vegetations  of  rheumatism  are,  in  our  opinion, 
often  much  more  chronic  than  is  generally  believed,  and  those 
who  investigate  them  from  this  point  of  view  will  find  in 
them  areas  of  necrotic  tissue  shut  off  by  scar  tissue — that  is, 
they  will  find  imperfect  healing.  We  believe  that  in  cases  of 
malignant  endocarditis  of  rheumatic,  origin  the  disease  has  been 
slightly  active  long  before  symptoms  call  attention  to  the 
serious  nature  of  the  disease.  This  link  in  the  chain  of  evidence 
is  difficult  to  get,  but  doubtless  it  will  be  obtained  by  clinicians 
who  keep  a  constant  watch  on  their  patients  who  leave  hospital 
with  rheumatic  heart  disease.  When  in  these  cases  the 
malignant  type  arises  it  is  not  necessarily  because  some  added 
infection  has  attacked  scar  or  sclerotic  tissue,  but  because  some 
agency  lowering  the  general  health  has  aroused  the  lurking 
micrococci  of  a  previous  infection  which  are  lying  in  the 
necrotic  areas  bordering  on  the  general  blood  stream. 

In  our  original  paper  u  we  could  not  hazard  how  many 
cases  of  malignant  endocarditis  were  rheumatic,  but  we 
thought  future  experience  would  show  that  a  very  considerable 


270  FURTHER  INVESTIGATIONS  UPON 

percentage  would  prove  to  be  of  this  type.  We  are  thus 
interested  to  find  a  writer  discovering  that  the  type  of  strep- 
tococcus most  often  found  in  infective  endocarditis  is  not  the 
highly  pathogenic  streptococcus  of  suppurative  processes,  but 
what  he  terms  "  one  or  other  of  three  types  of  streptococci  that 
are  more  closely  allied  to  the  '  saprophytic  '  streptococci  of  the 
alimentary  canal."  In  an  analysis  of  ioo  cases  of  infective 
endocarditis  we  also  note  that  he  finds  a  streptococcus  was 
present  in  62.  We  hold  that  all  complete  evidence  goes  to 
show  that  the  streptococcus  which  causes  acute  rheumatism 
is  a  cause  also  of  malignant  endocarditis,  and  that  the  further 
evidence  in  this  condition  of  the  frequent  occurrence  of 
"  streptococci,"  which  for  want  of  a  better  description  from 
others  we  may  call  peculiar,  is  an  additional  support  to  this  view. 
We  would  add  that  since  our  first  contribution  to  this 
question  we  have  seen  further  cases  in  adults  and  children 
which  confirm  our  original  examples  and  entirely  support 
the  view  that  rheumatism  may  be  a  cause  of  malignant 
endocarditis. 

Acute  Rheumatism  and  Rheumatic  Fever  Faulty  Terms 

The  next  point  we  would  emphasise  is  the  retarding  influence 
that  the  terms  acute  rheumatism  and  rheumatic  fever  exert 
upon  the  study  of  rheumatism.  If  we  compare  any  one  other 
great  infection  to  rheumatism  in  its  clinical  course  it  would  be 
tuberculosis.  This  is  but  a  repetition  of  a  former  statement, 
but  we  allude  to  it  now  because  it  is  so  thoroughly  supported 
by  a  recent  paper  by  Dr.  R.  Miller  12  upon  chorea.  In  this 
paper  the  writer  dwells  upon  the  fact  that  the  choreiform 
movements  are  but  the  developed  disease,  and  that  there  may 
be  warnings  weeks  before  these  appear.  The  late  Dr.  W.  B. 
Cheadle,  Sir  Thomas  Barlow,  and  Sir  Dyce  Duckworth  have 
called  attention  to  the  same  point.  This  premonitory  stage  is 
not  peculiar  to  chorea,  for  heart  disease  and  arthritis  show  the 
same  features.  Many  cases  in  childhood  which  develop  obvious 
rheumatism  may  suffer  for  some  weeks  from  fever,  anaemia, 
and  debility  before  anyone  can  foresee  the  exact  meaning  of 
these  symptoms,  a  point  which,  we  may  add,  Dr.  <G.  H.  M. 
Dunlop  has  also  insisted  upon.  How  can  we,  in  face  of  these 
facts,  keep  the  terms  acute  rheumatism  and  rheumatic  fever 
as  indicative  of  anything  but  phases  of  rheumatism  ?     We  have 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     271 

no  doubt  that  a  good  deal  of  the  mystery  of  unexplained  heart 
disease,  and  in  particular  mitral  stenosis,  is  the  result  of  this 
imperfect  naming  of  the  disease.  It  is  essential  that  some 
more  general  term  such  as  rheumatism,  which  implies  neither 
acuteness  nor  chronicity,  should  be  used. 

Rheumatic  Hyperpyrexia 

Hyperpyrexia  is  an  event  in  rheumatism  which  all  would 
point  to  as  one  which  should  throw  light  on  the  pathology  of 
the  disease.  Through  the  kindness  of  Dr.  Lauriston  Shaw  and 
Dr.  A.  F.  Hertz  we  have  had  assistance  from  Guj^'s  Hospital 
upon  this  question.  Until  this  recent  opportunity  we  had 
only  one  case  for  investigation,  and  that  not  a  classical 
example.  It  was  fully  published  by  us  in  the  Lancet  in  1905 
(Paper  No.  18) 13  and  was  peculiar  in  that  there  was  severe 
cerebro-spinal  meningitis.  In  the  exudation  there  were  great 
numbers  of  strepto-diplococci,  and  we  satisfied  ourselves  that 
it  was  a  rheumatic  case.  There  is  no  necessity  to-  recount  the 
details  of  that  investigation  here.  Our  second  from  Guy's  was 
of  the  classical  type,  the  patient,  an  adult,  dying  with  a 
temperature  of  107  °  F.,  and  the  post-mortem  examination 
showing  active  rheumatism  but  no  meningitis.  The  following 
details  give  the  salient  features  of  this  investigation. 

The  following  tubes,  among  others,  were  received  from 
Guy's  Hospital  on  August  13th,  1909  :  (1)  the  turbid  peri- 
cardial fluid  in  a  sterilised  pipette  ;  (2)  the  blood  ;  and 
(3)  portions  of  the  cerebral  cortex.  The  two  latter  were 
placed  in  bouillon.  The  pericardial  fluid  was  incubated  over- 
night without  addition  of  any  medium. 

The  following  results  were  obtained.  A  pure  growth  of 
strepto-diplococci  was  present  in  the  incubated  pericardial 
fluid.  The  cerebral  cortex  gave  a  growth  of  diplococci  with  a 
few  colonies  of  staphylococcus  aureus.  The  blood  gave  a 
growth  of  diplococci  and  bacillus  coli.  A  film  of  the  cerebro- 
spinal fluid  showed  a  few  diplococci.  A  film  of  the  pericardial 
fluid  showed  the  diplococci  in  streptococcal  chains  and  in 
considerable  number. 

On  August  15  two  intravenous  inoculations  were  made  into 
rabbits.  No.  1  received  30  drops  of  the  pericardial  fluid. 
No.  2  received  20  drops  of  the  bouillon  culture  from  the 
cerebral  cortex  which  contained  some  colonies  of  staphyl0- 


272  FURTHER  INVESTIGATIONS  UPON 

coccus  aureus  with  the  diplococcus.  The  second  rabbit  died 
in  24  hours  from  acute  pericarditis,  and  the  pericardial  fluid 
from  this,  incubated  overnight,  showed  a  pure  growth  of 
strepto-diplococci.  The  other  organs  showed  no  obvious 
change.  They  were  not  soft  and  there  were  no  haemorrhages. 
The  first  rabbit  lived  a  week  and  during  that  time  it  rapidly 
wasted  and  developed  pyrexia,  endocarditis,  and  arthritis  of 
the  right  knee-joint.  The  post-mortem  examination  showed 
early  endocarditis  of  the  tricuspid  valve,  a  fibrino -plastic 
exudation  in  the  right  knee-joint,  and  an  infarct  in  the  right 
kidney.  Cultures  from  the  right  knee-joint  gave  a  pure 
culture  of  strepto-diplococci. 

A  third  rabbit  was  inoculated  intravenously  with  10  minims 
of  the  incubated  pericardial  fluid  from  rabbit  No.  1.  Three 
days  later  there  was  arthritis  of  both  shoulder- joints  with 
wasting  and  general  illness,  but  during  the  next  week  there 
was  gradual  recovery  from  the  arthritis.  This  animal  died 
from  acute  intussesception  12  days  after  the  injection,  and  the 
post-mortem  examination  showed  no  cardiac  lesion  and  a 
healing  arthritis. 

A  fourth  rabbit  was  inoculated  on  August  25  with  a  culture 
from  the  cerebro-spinal  fluid.  On  the  28th  the  right  knee 
became  swollen  and  tender  and  the  animal  began  to  waste.  No 
cardiac  lesion  was  detected. 

Examination  of  fragments  of  the  aortic  and  mitral  valves, 
portions  of  the  motor  cortex  and  pia  mater  of  the  patient 
showed  that  the  valvular  lesions  were  of  old  standing  and 
that  the  brain  and  pia  mater  examined  only  showed  a  few 
diplococci. 

The  result  of  this  investigation  may  be  thus  summarised  : 
From  a  case  of  rheumatic  fever  with  carditis,  arthritis,  and 
hyperpyrexia  a  strepto-diplococcus  was  obtained  in  pure 
culture  direct  from  the  pericardial  fluid  incubated  overnight. 
This  strepto-diplococcus  produced,  on  intravenous  inoculation 
into  rabbits,  non-suppurative  multiple  arthritis,  pericarditis, 
endocarditis,  and  infarction,  and  the  micro-organism  was  again 
isolated  from  the  lesions  in  pure  culture.  The  same  micro- 
organism was  present  in  the  cerebro-spinal  fluid,  motor  cortex, 
and  blood  of  the  patient. 

It  would  be  a  mistake  to  infer  too  much  from  a  single  case, 
but  we  believe  this  investigation  supports  the  general  opinion 


'VB 


FIG.  84 

Incubated  human  pericardial  tiuid  (x  600)  from  a  case  of  rheumatic  pericarditis 

and  fatal  hyperpyrexia.  The  diplococcus  growing-  in  streptococcal  chains 


/i- 


fig.  85 

Incubated  pericardial  fluid  of  a  rabbit  dead  from  pericarditis  resulting  from  intravenous 
inoculation  with  the  diplococcus  isolatedfrom  the  case  of  rheumatic  hyperpyrexia.  (  x  1000.) 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     273 

among  physicians  that  rheumatic  hyperpyrexia  is  a  peculiar 
toxsemic  process  rather  than  an  intense  bacterial  invasion,  for 
although  the  micrococci  were  both  isolated  and  demonstrated, 
they  were  not  present  in  the  tissues  or  blood  in  any  extra- 
ordinary numbers. 

Investigations  upon  the  Tonsils  in  the  Rheumatic 

Two  other  lines  of  investigation  have  occupied  our  attention 
in  the  last  five  years  :  the  first  is  another  step  in  the  study  of 
the  tonsils  suggested  to  us  by  Mr.  George  Waugh  ;  the  second 
is  an  experimental  study  of  arthritis,  with  a  view  to  ascertain- 
ing whether  more  than  one  form  of  arthritis  may  result  from 
intravenous  inoculation  of  the  same  micro-organism.  The 
object  of  this  second  investigation  is  to  widen  the  field  of  study 
of  rheumatoid  affections,  reversing,  as  it  were,  the  usual  method 
of  inquiry.  The  clinician  seeks  among  this  heterogeneous 
group  to  find  some  one  clear  path.  We  have  started  along 
one  clear  path  (the  study  of  the  diplococcus)  and  endeavoured  to 
find  our  way  some  little  distance  into  this  heterogeneous  group. 

Taking  first  the  tonsils  in  rheumatic  fever  we  need  only 
mention  the  great  frequency  of  tonsillitis  in  this  disease,  and 
the  demonstration  by  Dr.  William  Hill 14  some  twenty  years  ago 
of  deep-seated  foci  of  disease  in  enlarged  tonsils  removed  from 
the  rheumatic.  In  1900  we  showed  that  a  micrococcus  found 
in  rheumatic  lesions  could  be  isolated  from  acute  rheumatic 
angina,  and  be  demonstrated  in  the  tonsils,  and  further  would 
produce  similar  lesions.  In  the  next  year  Fritz  Meyer  published 
an  extensive  paper  upon  the  same  subject,  and  we  have 
returned  to  the  question  again  to  work  out  Mr.  Waugh 's 
suggestion.  Mr.  Waugh  advocates  enucleation  of  the  large 
unhealthy  tonsils  that  are  so  often  present  in  rheumatic 
children,  and  in  some  carefully  chosen  cases  has  done  this  for 
us  between  the  rheumatic  attacks.  These  tonsils  were  seared 
on  removal,  cultures  were  taken  from  their  depths,  and  the 
histological  appearances  of  them  investigated.  One  example 
will  suffice  to  show  the  kind  of  case  investigated,  six  of  which 
have  been  examined  up  to  the  present  date. 

The  patient,  a  male  aged  10  years  and  5  months,  came  to 
the  Hospital  for  Sick  Children,  Great  Ormond  Street,  in 
February  1908,  suffering  from  slight  chorea  and  rheumatic 
pains.     In  1906  he  had  an  attack  of  rheumatic  fever,  since 

18 


274  FURTHER  INVESTIGATIONS  UPON 

which  he  had  never  quite  recovered  his  usual  health,  and  had 
always  had  shortness  of  breath  on  exertion.  The  heart  was 
obviously  affected.  There  was  considerable  mitral  regurgita- 
tion, with  hypertrophy  and  dilatation.  In  addition  he  had 
two  very  large  tonsils  and  was  subject  to  sore-throats.  The 
cervical  glands  showed  a  moderate  enlargement.  In  April, 
when  quite  recovered  from  his  active  rheumatism,  Mr.  Waugh 
enucleated  both  tonsils.  Immediately  after  removal  the 
surface  was  seared,  and  cultures  were  taken  from  the  centre  of 
one  gland.  Histological  examination  by  section  and  films  of 
the  other  tonsil  showed  the  presence  of  streptococci  in  the  deep 
part  of  the  gland.  The  culture  gave  an  almost  pure  growth 
of  strepto-diplococci,  from  which  it  was  easy  to  isolate  this 
organism  in  pure  culture.  Five  minims  of  this  culture  injected 
intravenously  into  a  rabbit  produced  no  result.  Two  cubic 
centimetres  produced  arthritis  and  fatal  aortic  endocaraitis. 
One  cubic  centimetre  in  another  experiment  produced  arthritis 
of  the  left  knee,  which  slowly  recovered.  Subsequently  smaller 
doses  produced  arthritis  of  the  right  knee-joint  and  fatal 
endocarditis. 

We  have  here  but  a  repetition  of  the  results  obtained  in  our 
original  case  in  1899,  and  independently  confirmed  by  Fritz 
Meyer15  in  1901.  The  particular  point  of  interest  lies  in  the 
fact  that  here  we  are  dealing  with  tonsils  in  the  rheumatic 
when  they  are  not  in  the  stage  of  acute  inflammation,  during 
an  attack  of  acute  rheumatism,  but  in  the  latent  period  after 
previous  attacks  of  the  disease. 

There  can  be  very  little  doubt,  we  believe,  that  these  large 
unhealthy  tonsils  are  a  constant  menace  to  the  rheumatic, 
and  that  these  investigations  originated  by  Mr.  George  Waugh 
show  decisively  that  there  abound  in  the  depths  of  these  dis- 
ordered tissues  strepto-diplococci  which  will  produce  with 
much  constancy  in  appropriate  dosage  endocarditis,  peri- 
carditis, and  arthritis  on  intravenous  injection  into  rabbits. 
We  believe  they  may  well  explain  some  rheumatic  relapses. 
The  relation  of  acute  rheumatism  and  tonsillitis  to  the 
diplococcal  infection  is  now  so  well  defined  by  clinical  observa- 
tion, histological  investigation,  and  experimental  research  that 
it  constitutes  one  of  the  most  satisfactory  advances  in  the 
study  of  the  disease.  We  have  only  to  contrast  the  explanation 
it  gives  us  with  the  older  nervous  and  lactic  acid  theories  to 


276  FURTHER  INVESTIGATIONS  UPON 

recorded  example  of  experimental  osteo-arthritis  by  intra- 
venous inoculation.  Since  that  date  we  have  produced  osteo- 
arthritis ana  peri-articular  arthritis  with  the  diplococcus 
rheumaticus,  and  at  the  present  time  we  have  a  very  striking 
specimen  of  an  arthritis  resulting  from  this  infection.  This 
occurred  in  a  rabbit  which  had  developed  inflammation  first 
of  one  knee-joint  and  then  of  the  other,  from  which  it  gradually 
recovered,  but  eighteen  months  later,  though  in  good  health,  it 
limped  to  some  extent  upon  the  hind  limbs.  This  specimen 
showed  that  there  was  a  clear  fluid  in  both  articulations,  but 
the  right  patella  was  dislocated  and  had  formed  for  itself  a 
new  facet  on  the  inner  side  of  the  internal  femoral  condyle  and 
the  original  facet  had  lost  much  of  its  cartilage,  and  the  bones 
had  been  eroded.  The  left  joint  showed  erosion  of  cartilage. 
This  specimen  is  in  the  museum  of  the  Royal  College  of 
Surgeons.  The  occurrence  of  dislocations  of  joint  surfaces  in 
human  "  rheumatoid  arthritis  "  is  well  recognised,  and  the 
production  of  such  a  deformity  is  strictly  analogous  to  the 
condition  in  the  specimen  just  described,  in  that  there  are  in 
both  a  stretching  and  damaging  of  the  capsules  of  the  articula- 
tions by  a  non-suppurative  process,  a  damage  to  the  articulating 
surfaces  themselves,  and  a  faulty  pull  of  tendons  connected 
with  the  joints.  At  the  British  Medical  Association  meeting 
at  Manchester  we  also  demonstrated  convincing  examples  of 
the  "  guttering  "  of  osteo-arthritis,  and  published  illustrations 
of  these  changes  in  a  paper  in  the  Medical  Press  and  Circular}1 
In  this  paper  we  also  showed  that  perivascular  fibrosis  occurred 
in  the  capsules  of  articulations,  the  subject  of  experimental 
and  pathological  chronic  arthritis,  explaining  thereby  the 
"  withering  "  of  joints  in  rheumatoid  affections.  We  have 
also  produced  that  rarefying  osteitis  of  bone  ends  in  the  neigh- 
bourhood of  joints  affected  by  chronic  disease  which  is  well 
recognised  in  "  rheumatoid  arthritis." 

In  conclusion,  we  would  repeat  that  no  explanation  of 
acute  rheumatism  can,  we  believe,  compare  with  that  which 
attributes  it  to  an  infection  with  a  diplococcus  of  the  strepto- 
coccal group  ;  and  that  although  during  the  last  ten  years 
this  view  has  gained  but  little  headway  in  this  country  the 
Chelsea  Clinical  Society  in  1900  marked  a  forward  step  in 
London  when  they  opened  a  discussion  on  "  Acute  Infective 
Rheumatism." 


THE  PATHOLOGY  OF  RHEUMATIC  FEVER     277 


REFERENCES 

1  Lancet,  September  22  and  29,  1900. 

2  Ainley  Walker,  Practitioner ,  1903. 

3  Vernon  Shaw,  Journal  of  Pathology  and  Bacteriology,  1903. 

4  Beattie,  Brit.  Med.  Jour.,  December  1904  ;  Journal  of  Experimental 
Medicine,  vol.  ix,  No.  2,  1907. 

5  Transactions   of  the  Pathological  Society  of  London,  1901.    Lancet, 
May  4,  1 90 1. 

6  La  Tribune  Medicate,  February  26,  1910,  p.  134. 

7  Poynton,  Transactions  of  the  Royal  Medical  and  Chirurgical  Society, 
vol.  lxxxii,  1899. 

8  Transactions  of  the  Pathological  Society  of  London,   1901  ;    Inter- 
national Clinics,  vol.  iii,  Series  13. 

9  Brit.  Med.  Jour.,  1906,  vol.  ii,  p.  1103. 

10  Quarterly  Journal  of  Medicine,  vol.  ii,  No.  5. 

11  Transactions  of  the  Royal  Medical  and  Chirurgical  Society,   vol. 
lxxxv,  1903. 

12  Lancet,  December  18,  1909,  p.  1808. 

13  Lancet,  December  16,  1905,  p.  1761. 

14  "  Tonsillitis  in  Rheumatic  States,"  1889. 

15  A  paper  read  before  the  Congress  of  Internal  Medicin,  Berlin,  1901:. 

16  Transactions  of  the  Pathological  Society  of  London,  1902. 

17  Medical  Press  and  Circular,  April  5,  1907. 


PART  II 

SUB-GROUP  E 

THE  THREE  PAPERS  IN  THIS  SUB-GROUP  ARE  IN  THE 
MAIN  CLINICAL  IN  CHARACTER,  THE  FIRST  TWO 
DEALING  RESPECTIVELY  WITH  RHEUMATISM  IN 
VERY  EARLY  LIFE  AND  WITH  THE  ASSOCIATION 
OF  SCARLET  FEVER  AND  RHEUMATISM.  THE  THIRD 
PAPER  TREATS  IN  PARTICULAR  OF  RHEUMATIC 
HEART  DISEASE  AS  AN  EVENT  IN  THE  HISTORY 
OF  AN  INFECTIVE  PROCESS  RATHER  THAN  AS  A 
PARTICULAR  FORM  OF  CARDIAC  AFFECTION 

XXL  A  CONTRIBUTION  TO  THE  SUBJECT  OF  RHEUMA- 
TISM BASED  UPON  THE  STUDY  OF  FIFTY -TWO 
CASES  IN  CHILDREN  UNDER  FIVE  YEARS  OF  AGE, 
AND  AN  ANALYSIS  OF  ONE  HUNDRED  CASES  OF 
SUPPURATIVE  PERICARDITIS  IN  CHILDHOOD 

XXII.  A  CONTRIBUTION  TO  THE  STUDY  OF  RHEUMATISM, 
WITH  NOTES  ON  THE  AFTER-HISTORY  OF  TWENTY- 
FIVE  CASES  OF  "  SCARLATINAL  RHEUMATISM  " 

XXIII.  A  RESEARCH  UPON  COMBINED  MITRAL  AND  AORTIC 
DISEASE  OF  RHEUMATIC  ORIGIN.  A  CONTRIBUTION 
TO  THE  STUDY  OF  MALIGNANT  RHEUMATIC  ENDO- 
CARDITIS 


$79 


PAPER  NO.  XXI 

A  CONTRIBUTION  TO  THE  SUBJECT  OF  RHEU- 
MATISM BASED  UPON  A  STUDY  OF  FIFTY- 
TWO  CASES  IN  CHILDREN  UNDER  FIVE 
YEARS  OF  AGE,  AND  AN  ANALYSIS  OF 
ONE  HUNDRED  CASES  OF  FATAL  SUP- 
PURATIVE PERICARDITIS  IN  CHILDHOOD 

(Reprinted  from  the  Quarterly  Journal  of  Medicine,  April  1908) 

This  short  clinical  paper  demonstrates  that  acute  rheumatism  is  not 
infrequent  at  five  years  and  even  under  that  age.  The  suggestion  that 
there  is  any  peculiarity  in  the  age  incidence  of  this  disease  which 
militates  against  the  theory  of  its  infective  origin  is  thus  disposed  of, 
and  its  identity  at  this  age  with  the  condition  in  later  life  established. 
Finally,  a  study  of  pneumococcic  pericarditis  gives  a  striking  proof  of 
the  great  differences  in  the  effects  of  the  pneumococcic  and  rheumatic 
infections  upon  the  heart,  and  shows  that,  though  the  diplococcus  of 
rheumatism  in  vitro  would  appear  to  be,  in  some  respects,  closely  akin 
to  the  pneumococcus,  yet  in  their  pathogenic  properties  in  the  human 
tissues  these  micrococci  are  essentially  different. 

There  has  been  a  good  deal  of  difference  of  opinion  expressed 
by  writers  as  to  the  frequency  of  acute  rheumatism  in  children 
under  five  years  of  age.  Some  have  maintained  that  it  is  an 
exceedingly  rare  occurrence,  while  others  have  doubted  this. 
The  question  is  one  of  theoretical  and  practical  import- 
ance, and  this  is  the  excuse  for  putting  on  record  here  our 
own  experience  as  a  contribution  to  the  subject  of  acute 
rheumatism. 

The  theoretical  interest  lies  mainly  in  our  conception  of  the 
cause  of  acute  rheumatism,  or,  as  we  would  prefer  to  call  it, 
rheumatism.  If,  as  one  is  now  almost  compelled  to  admit, 
there  is  an  infective  agent,  or,  in  the  opinion  of  many,  more 
than  one,  which  determines  the  active  disease,  it  is  difficult  to 

2S1 


282  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

understand  why,  during  the  first  five  years  of  life,  the  occur- 
rence of  the  infection  should  be  very  unusual.  It  may  be 
reasonably  admitted  that  prior  to  school  life  there  is  less 
exposure  to  the  infection,  but  even  then,  one  can  hardly  help 
believing  that  a  sufficient  number  of  cases  must  be  met  with 
to  enable  us  to  recognise  that  rheumatism  does  not  make  a 
mysterious  appearance  at  any  particular  age,  but  is 
throughout  life  a  menace  to  some  constitutions.  If  this 
should  prove  to  be  the  case,  it  will  help  us  to  bring  the 
rheumatic  infection  into  line  with  such  other  great  infections 
as  the  pneumococcic  and  tubercular. 

In  a  symposium  upon  rheumatic  fever  in  childhood,  the 
result  of  a  recent  Congress  in  America,  we  find  one  writer  has 
the  hardihood  to  suggest  that  in  England  a  disease  in  children 
has  been  manufactured  which  we  call  rheumatism,  by  fitting 
together  all  manner  of  divers  symptoms.  This  procedure, 
according  to  him,  has  been  adopted  to  account  for  the  disease 
up  to  the  age  of  twelve  years  !  No  one  in  this  country  has 
any  qualms  as  to  the  reality  of  the  disease  from  five  to  twelve 
years,  and  this  unguarded  writing  can  only  be  a  warning  to 
those  who  live  in  a  different  country  and  attempt  to  criticise 
the  clinical  acumen  of  physicians  who  have  special  advantages 
in  any  particular  line  of  investigation. 

In  rheumatism  at  this  early  age  there  are  several  points  of 
practical  interest.  The  question  of  diagnosis  is  one,  for  under 
five  years  of  age  such  widely  different  disorders  as  scurvy, 
anterior  poliomyelitis,  spinal  caries,  congenital  syphilis,  gono- 
coccic  and  meningococcic  arthritis,  congenital  heart  disease, 
influenzal  and  pneumococcic  septicaemia  come  into  the  field  of 
discussion.  This  particular  aspect  of  the  question  we  shall 
not  consider  here,  for  it  is  dealt  with  in  many  books. 

Another  point  is  the  clinical  character  of  the  disease  at  this 
early  age.  Shall  we  find  this  unusual,  or  closely  resembling 
the  character  in  later  childhood  and  adolescence  ?  The  death 
rate,  the  percentage  of  cardiac  affections,  and  the  liability  to 
relapse,  are  other  details  of  importance. 

Lastty,  shall  we  be  led  from  a  study  of  such  cases  to  the 
view  that  rheumatism  is  not  an  entity,  because  we  find  that  at 
this  age  its  differentiation  from  other  infections  becomes  so 
difficult  as  to  degenerate  into  a  mere  academic  splitting  of 
hairs  ?     Upon  this  point  we  have  been  at  some  pains  to  collect 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  283 

for  comparison  100  fatal  cases  of  suppurative  pericarditis 
under  twelve  years,  mostly  the  result  of  pneumococcic  infec- 
tion. Our  object  has  been  to  study  side  by  side  with  rheu- 
matism, which  we  regard  as  an  entity,  an  infection  which 
approaches  it  bacteriologically  and  clinically. 

There  are  52  cases  of  rheumatism  in  children  under  five 
recorded  in  this  paper.  Many  of  the  notes  are  fragmentary. 
They  have,  however,  this  value,  that  they  are  all  personal 
observations,  not  one  is  taken  from  hearsay  evidence,  and  as 
such  they  assist  in  establishing  the  main  thesis  of  the  paper, 
that  the  frequency  of  rheumatism  in  children  under  five  is 
sufficient  to  make  one  believe  that  it  obeys  the  laws  of  other 
great  infections. 

To  these  52  cases  are  appended  17  others.  These  are  older 
children,  who  have  come  with  rheumatism,  and  whose  parents 
have  given  a  history  of  an  earlier  attack  before  the  age  of  five. 
In  the  case  of  chorea,  the  evidence  when  repeated  in  several 
instances  is  very  suggestive  of  truth,  for  chorea  makes  a  deep 
impression  upon  the  minds  of  parents.  The  52  cases,  and 
17  presumptive  ones,  are  placed  in  appendices  at  the  end  of 
the  paper,  and,  in  order  to  avoid  wearisome  reiteration,  the 
chief  points  that  they  illustrate  are  considered  in  the  short 
summaries  that  follow.  There  can  be,  we  think,  no  doubt 
that  the  fact  that  we  have  been  able  to  collect,  in  a  desultory 
fashion,  52  examples  of  rheumatism  under  five  years,  all  of 
which  have  been  under  personal  supervision,  settles  the  question 
that  rheumatism  resembles  other  great  infections  in  having  no 
mysterious  age  limit. 

It  is  equally  clear  that  the  disease  before  the  age  of  five  years 
resembles  very  closely  the  condition  from  five  years  to  adoles- 
cence, for  if  we  take  these  52  cases  and  choose  those  manifesta- 
tions of  acute  rheumatism  that  are  generally  accepted  as 
cardinal,  such  for  example  as  heart  disease,  arthritis,  chorea, 
sore  throat,  and  nodules,  we  find  the  following  figures  : 

Definite  heart  disease       .  .  .  in  43  cases 

Arthritis  or  arthritic  pains  .  .  in  35     „ 

Chorea  .         .         .  .  .  in  18     „ 

Sore  throat     .         .         .  .  .  in  10     „ 

Nodules  .         .         .  .  .  in    8     ,, 

The  mortality  is  high  at  this  early  age.     Eight  died,  and 


284  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

five  more  were  in  a  hopeless  condition.  Twenty-two  made 
partial  recoveries  with  permanently  damaged  hearts,  and 
among  these  it  is  more  than  probable  that  some  succumbed 
later  to  further  attacks. 

A  terminal  pericarditis  was  present  in  seven  out  of  the  eight 
fatal  instances,  and  there  were  in  these  cases  many  other 
manifestations  of  rheumatism,  the  disease  generalising  as  it 
does  in  other  infections  in  childhood.  Yet,  in  spite  of  the 
systemic  involvement  and  terminal  pericarditis,  it  was  im- 
possible to  mistake  the  condition  for  any  other  than  rheu- 
matism. In  support  of  this  we  submit  the  analysis  of  100 
cases  of  suppurative  pericarditis  in  childhood,  the  great 
majority  of  which  were  pneumococcic  in  origin.  In  15  of 
these  the  bacteriological  nature  of  the  condition  was  accurately 
ascertained  as  pneumococcic.  Eight  were  probably  not  of 
this  nature,  being  associated  with  acute  osteo-myelitis,  otitis 
media,  and  suppurating  wounds,  and  in  these  there  were 
multiple  pyaemic  abscesses. 

One  example  of  a  characteristic  case  will  throw  into  relief 
the  differences  in  the  clinical  course  of  a  rheumatic  and  pneu- 
mococcic pericarditis.  A.  C,  a  female  aged  2^z  years,  had 
suffered  for  several  weeks  from  whooping  cough,  followed  by 
pneumonia.  YMien  she  came  under  observation  she  was  very 
cyanosed  and  dyspricec.  Respiration  was  panting,  and  there 
was  irregular  fever.  Both  sides  of  the  chest  showed  signs  of 
effusion,  and  later  in  the  illness  the  cardiac  dullness  was  found 
increased,  and  the  sounds  were  noted  to  be  faint.  Double 
empyema  was  diagnosed  and  suppurative  pericarditis  sus- 
pected. Death  occurred  rapidly,  and  i-l-  ounces  of  pus  were 
found  in  the  pericardium,  together  with  pus  in  both  pleurae. 
The  pnenmococcus  was  isolated  from  the  effusion.  Thus,  in 
this  case,  associated  with  this  form  of  pericarditis,  there  were 
purulent  pleural  effusions,  but  there  w7as  no  arthritis,  and,  still 
more  striking,  there  was  no  endocarditis. 

Rheumatic  pericarditis  is,  on  the  whole,  easy  of  diagnosis, 
but  fewT  conditions  are  more  difficult  to  detect  than  suppurative 
pericarditis.  In  only  six  of  the  100  cases  was  it  detected  with 
certainty,  and  two  of  these  showed  the  rare  symptom  in 
suppurative  pericarditis  of  pericardial  friction. 

The  reasons  for  the  difficulty  in  diagnosis  help  us  to 
emphasise  the  distinctions  between  rheumatic  and  pneumococcic 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  285 

pericarditis.  Thus  the  occurrence  of  friction  in  two  percent,  of 
the  latter  series  is  a  very  different  experience  to  its  frequency 
in  the  rheumatic  form. 

The  absence  of  endocarditis  is  even  more  remarkable,  only 
one  per  cent,  of  the  pneumococcic  showed  any  valvular  lesion. 
Again,  in  only  one  of  these  cases  was  pericarditis  the  out- 
standing lesion.  Three  others  showed  evidence  of  old  pul- 
monary disease.  Fifty-four  were  associated  with  an  empyema 
on  one  or  both  sides,  and  31  with  acute  pleurisy  or  pneumonia. 
Two  were  complicated  by  acute  pulmonary  tuberculosis,  and 
eight  with  septic  broncho-pneumonia. 

Pleurisy  and  broncho-pneumonia  are  met  with  in  virulent 
rheumatic  heart  disease,  but  it  is  quite  the  exception  and  not 
the  almost  invariable  rule  for  the  pulmonary  lesions  to  dominate 
in  the  clinical  picture. 

Couple  this  with  the  fact  that  in  an  analysis  of  150  cases  of 
fatal  rheumatism  under  twelve  years,  149  showed  a  valvular 
lesion,  and  we  doubt  whether  two  more  striking  proofs  of  the 
specific  differences  in  these  infections  could  be  possible. 

Nevertheless,  if  we  turn  to  the  age  incidence,  we  find  the 
most  convincing  additional  evidence.  In  the  pneumococcic 
series  84  per  cent,  occurred  before  the  child  reached  the  fourth 
year,  and  66  per  cent,  between  the  ages  of  one  and  three  years. 
Rheumatic  pericarditis,  as.  shown  by  these  52  cases,  certainly 
occurs  with  some  frequency  under  five,  but  this  frequency 
rises  rapidly,  with  the  incidence  of  rheumatism,  up  to  the  age 
of  ten.  Pneumococcic  pericarditis  followed  measles  in  12 
instances  ;  the  rheumatic  is  more  closely  associated  with 
scarlet  fever. 

These  fatal  cases  of  pneumococcic  pericarditis  also  bring  out 
clearly  that  rheumatic  pericarditis  cannot  be  looked  upon  as 
a  peculiar  phase  of  those  infections  which  produce  suppuration, 
using  that  term  in  its  everyday  sense.  For  if  we  first  consider 
rheumatic  pericarditis  we  find  an  acutely  virulent  haemorrhagic 
form,  a  severe  form  in  which  occurs  an  exudation,  which  we 
consider  a  rheumatic  suppuration,  a  mild  form  with  a  clear 
exudation,  and,  lastly,  a  smouldering  fibrino-plastic  one. 

If  we  consider  the  pneumococcic  pericarditis  we  find  the 
same  variety  of  processes.  There  are  the  fulminating  types, 
the  severe  ones  with  profuse  suppuration,  the  milder  ones  with 
a  more  fibrinous  exudation,   and  the  undoubtedly  rare  but 


286  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

definite  cases  in  which  there  is  a  partial  organisation  of  a 
chronic  inflammatory  exudation. 

Although  the  difficulty  in  the  diagnosis  of  suppurative 
pericarditis  is  almost  insurmountable,  and  for  this  reason  it 
becomes  a  practical  impossibility  to  date  the  exact  time  of  its 
onset  during  the  course  of  an  acute  illness,  nevertheless  the 
post-mortem  records  show  that  this  pericarditis  may  last  many 
weeks  before  proving  fatal,  and  the  illnesses  associated  with 
this  condition  may  be  grouped  into  three  classes  : 

1.  The  acute,  running  a  course  of  about  four  weeks.  This 
included  twenty  cases  of  the  series. 

2.  The  sub-acute,  lasting  from  four  weeks  to  six  months. 
Representing  50  cases. 

3.  The  chronic,  with  insidious  onset,  lasting  from  six  months 
to  one  year.     Representing  17  cases. 

It  is  clear  that  both  rheumatic  and  pneumococcic  peri- 
carditis show  variations  in  virulence  but  it  cannot  be  accepted 
that  the  rheumatic  form  is  a  phase  of  the  pneumococcic. 

Such  clinical  and  pathological  facts  as  these  are  far  more 
convincing  evidence  of  the  specific  nature  of  rheumatism  than 
are  the  evidences  of  laboratory  tests  against  its  specificity,  for 
they  represent  the  behaviour  of  the  infective  agent  in  the  media 
of  the  human  tissues,  which  are  the  media  with  which  we  are 
concerned  in  human  diseases.  In  conclusion,  we  would  hold 
that  rheumatism,  though  unusual,  is  by  no  means  rare  under 
five  years,  and  that  its  study  strongly  supports  the  specific 
nature  of  the  infection. 

Appendix  I 

Fifty-two  cases  of  Rheumatism  under  five  years  of  age 

Case  i.  January  1899.  T.  W.,  male,  aged  4^  years. 
Two  weeks  previously  he  had  complained  of  pains  in  the  knees, 
followed  by  chorea.  When  first  under  observation  there  was 
moderate  general  chorea  and  early  mitral  disease.  A  severe 
attack  resulted,  but  there  was  a  partial  recovery  and  the  child 
was  able  to  get  about  again.  In  November  1899,  there  was  a 
severe  relapse  with  fresh  cardiac  involvement  and  nodules, 
with  wasting.  This  case  was  lost  sight  of,  but  the  condition 
was  practically  a  hopeless  one. 

Summary  :  Relapsing  rheumatism ;  arthritis  ;  morbus 
cordis  ;   chorea  ;  nodules  ;   outlook  hopeless. 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  287 

Case  2.  October  1S99.  E.  S.,  female,  aged  4  years.  A 
vague  history  of  some  weeks,  in  which  pains  in  the  joints  were 
complained  of,  and  breathlessness  noticed.  There  was  a  family 
history  of  rheumatism.  This  child  had  organic  mitral  disease. 
A  good  recovery  followed.     She  was  lost  sight  of. 

Summary  :  Arthritic  pains  and  heart  disease  ;  good  recovery. 

Case  3.  November  1899.  M.P.,  male,  aged  3T^-  years. 
This  child  had  been  living  on  the  ground  floor  in  a  damp  house, 
and  was  brought  for  chorea,  which  had  been  preceded  by  a 
sore  throat.  When  first  seen  there  were  marked  anaemia, 
chorea,  and  dilatation  of  the  heart.  After  an  illness  of  four 
months  there  was  recovery  with  a  mitral  lesion.  She  was  lost 
sight  of. 

Summary  :  Anaemia  ;  chorea  ;  morbus  cordis  ;  sore  throat ; 
recovery. 

Case  4.  March.  1900.  G.  M.,  male,  aged  4^-  years.  His 
father  had  suffered  from  rheumatic  fever.  There  was  a  history 
of  some  weeks  of  debility,  wasting,  and  anaemia,  followed  by 
slight  chorea.  When  first  under  observation  there  was,  in 
addition,  dilatation  of  the  heart.  This  patient  made  a  good 
recovery. 

Summary  :  Anaemia  ;  chorea  ;  cardiac  dilatation  ;  recovery. 

Case  5.  September  1900.  J.  M.,  male,  aged  3^-  years. 
Some  weeks  before  coming  under  observation  this  child  was 
reported  to  have  caught  cold  and  developed  a  sore  throat. 
There  followed  multiple  arthritis,  the  ankles  being  first 
affected.  When  first  seen  there  were  multiple  arthritis,  pro- 
found anaemia,  mitral  and  aortic  disease,  but  no  nodules.  The 
temperature  was  only  just  above  normal.  Whilst  under 
observation  there  was  slight  epistaxis,  and  later  pleuro- 
pericarditis.  The  child  died  in  February  1901,  of  heart 
disease.      A  post-mortem  examination  was  refused. 

Summary  :  Sore  throat ;  morbus  cordis  ;  anaemia  ;  epistaxis  ; 
arthritis  ;   death,  after  pleuro-pericarditis. 

Case  6.  January  1901.  W.  G.,  male,  aged  2\  years.  This 
child  had  already  been  ill  for  seven  months.  The  onset  had 
been  with  pains  in  the  joints  and  swelling  of  the  knees  and 
ankles.  The  doctor  in  attendance  had  called  it  rheumatic 
fever.  When  we  saw  the  child  he  was  suffering  from  severe 
mitral  disease,  with  both  dilatation  and  hypertrophy.  His 
brother,  whom  we  also  saw  in  his  illness,  was  suffering  from 


288  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

unequivocal  rheumatism.  These  patients  were  only  brought 
for  an  opinion,  and  were  not  seen  again,  but  the  child  was 
undoubtedly  damaged  for  life. 

Summary  :  Arthritis  ;   morbus  cordis  ;   outlook  bad. 

Case  7.  March  1901.  E.  H.,  female,  aged  4^  years.  This 
was  a  very  instructive  example  of  the  danger  of  rheumatism. 
Three  months  before,  without  a  single  definite  symptom,  she 
was  noticed  to  be  getting  pale  and  progressively  feebler.  The 
first  distinct  warning  was  the  occurrence  of  slight  choreic 
twitchings.  When  first  under  observation  there  was  striking 
muscular  feebleness.  The  heart  was  feeble  and  dilated  and 
the  sounds  faint.  Soft  pericardial  friction  was  audible.  No 
nodules  were  present.  Fourteen  days  later  thrombosis  occurred 
in  the  left  jugular,  and  the  child  died  on  March  23.  The  post- 
mortem examination  showed  pericarditis,  multiple  endo- 
carditis, pleurisy,  and  broncho-pneumonia. 

Summary :  Anaemia  ;  broncho-pneumonia ;  carditis  ;  chorea  ; 
pleurisy  ;  venous  thrombosis  ;  death  ;  post-mortem  examina- 
tion. 

Case  8.  August  190 1.  J.  O.,  male,  aged  4^-  years.  Came 
under  observation  for  arthritis.  His  mother  had  suffered  from 
rheumatic  fever.  His  first  attack  of  arthritis  was  in  January 
1 90 1,  affecting  the  ankles  and  feet.  This  attack  was  followed 
by  another  in  March,  and  a  third  in  May.  The  fourth  attack, 
in  August,  involved  the  metacarpo-  and  metatarso-phalangeal 
joints  and  both  knees.  There  was  irregular  fever,  with  enlarge- 
ment of  the  glands  in  the  axillae  and  groins.  The  splenic 
dullness  was  also  increased.  Later,  more  of  the  smaller  joints 
were  involved,  and  the  neck  and  back  became  stiff.  The  heart 
was  dilated,  but  there  was  no  murmur.  This  case  went  from 
bad  to  worse,  and  extreme  emaciation  was  a  prominent  feature. 
Eventually  the  parents  took  him  away  in  disgust.  A  year 
later  on  inquiry,  expecting  to  hear  that  the  child  had  died,  the 
parents  informed  us  that  after  four  months  in  bed,  and  treat- 
ment by  cod  liver  oil,  he  improved,  and  was  now  able  to  go  to 
school.  Later  they  brought  him  and  we  found  the  enlarged 
glands  were  now  normal,  as  also  the  splenic  dullness.  The 
cervical  spine  was  rigid  and  flexed,  and  there  was  considerable 
periarticular  thickening  round  the  wrists.  Both  knee  joints 
were  enlarged  and  creaked  on  movement.  More  remarkable 
still  was  obvious  heart  disease.     A  loud  mitral  systolic  murmur 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  289 

was  audible,  and  the  left  ventricle  was  hypertrophied  and 
dilated.  In  1902  there  was  another  attack  of  arthritis.  In 
March  1903,  he  was  again  brought  very  ill.  His  head  was 
bent  almost  on  to  his  chest,  and  his  neck  was  swollen  and  stiff. 
The  wrists,  knees,  and  fingers  were  greatly  swollen,  and  his 
arms  terribly  wasted.  His  heart  was  greatly  enlarged,  the 
liver  reached  the  umbilicus,  and  there  was  ascites.  In  De- 
cember 1903,  he  was  still  living,  but  later  inquiries  failed  to 
bring  any  reply,  and  there  is  little  doubt  that  he  must  have 
died.  This  was  a  most  unusual  case,  and  possibly  not  rheu- 
matic. In  some  respects  it  resembled  Still's  syndrome,  and  in 
others  "rheumatoid  arthritis."  There  was,  nevertheless,  no 
scientific  objection  to  the  explanation  of  all  the  symptoms  as 
those  of  intractable  rheumatism.  Such  a  case  has  clearly 
strong  bearing  upon  the  whole  problem  of  the  relation  of 
rheumatism  to  rheumatoid  arthritis. 

Summary  :  Repeated  arthritis  periarticular  in  type  ;  heart 
disease  ;  emaciation  ;  enlarged  glands  and  spleen. 

Case  9.  June  1901.  Male,  aged  4-^-  years.  The  illness 
had  commenced  a  week  before  with  tired  feelings  and  pain  in 
the  limbs,  followed  by  diarrhoea  and  sickness.  There  was  a 
history  of  rheumatic  fever  in  the  father's  family.  He  was 
very  ill  and  pale.  His  throat  was  reddened,  and  there  was 
arthritis  of  both  knees.  The  heart  was  dilated,  and  a  systolic 
mitral  murmur  was  audible,  and  was  conducted  into  the  left 
axilla.  Five  days  later  he  developed  acute  pericarditis  and 
pneumonia  and  died  in  three  days.  The  post-mortem  showed 
arthritis,  early  pericarditis,  mitral  endocarditis,  a  large  spleen, 
and  broncho-pneumonia.  The  diplococcus  was  isolated  from 
the  pericardial,  cerebro-spinal,  pleural,  and  arthritic  exudations. 
This  case  died  in  three  weeks. 

Summary :  Sore  throat  ;  anaemia ;  carditis  ;  broncho- 
pneumonia ;  death. 

Case  10.  October  1901.  H.  C,  female,  aged  4^|  years. 
Fourteen  days%  before  she  had  a  sore  throat,  followed  by 
multiple  arthritis  and  heart  disease.  This  child  died  in 
December  of  heart  disease. 

Summary  :  Sore  throat ;  carditis  ;  arthritis  ;  death. 

Case  11.  December  190 1.  G.  P.,  male,  aged  4  years.  The 
mother  had  rheumatic  fever.  The  child  was  brought  for  heart 
disease.     There  was  advanced  mitral  disease,  and  none  of  the 

19 


29o  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

ordinary  evidences  of  congenital  heart  disease  ;  on  the  other 
hand  we  could  find  no  other  proof  of  rheumatism.  This  case 
was  lost  sight  of. 

Summary  :   Heart  disease. 

Case  12.  January  1902.  A.  H.,  female,  aged  10  months. 
The  father  had  rheumatic  fever.  At  eight  months  she  de- 
veloped chorea.  When  seen,  she  had  general  chorea  of 
moderate  severity.  The  heart  was  dilated,  and  there  was 
a  soft  systolic  mitral  murmur.  This  case  ran  a  favourable 
course.  The  chorea  disappeared  in  four  weeks,  and  the 
dilatation  of  the  heart  recovered,  the  murmur  disappearing. 
At  no  time  was  there  arthritis. 

Summary  :  Chorea  ;  cardiac  dilatation  ;  recovery. 

Case  13.  February  1902.  G.  S.,  female,  aged  4^  years. 
Four  months  before  coming  under  observation  she  had  suffered 
from  multiple  arthritis,  and  an  illness  which  the  doctor  in 
attendance  called  rheumatic  fever.  The  arthritis  subsided  in 
all  joints  but  the  knees,  which  remained  obstinate  and  full  of 
fluid.  Her  heart  was  dilated,  and  the  first  sound  short  and 
feeble.  Energetic  treatment  with  salicylates  had  failed  and 
contractures  were  commencing.  On  stopping  all  salicylates, 
feeding  abundantly  and  giving  quinine,  there  was  steady 
improvement.  The  irregular  fever  present  subsided,  and  in 
three  months  there  was  complete  recovery.  During  this 
period  a  small  firm  nodule  appeared  on  the  lower  end  of  the 
left  radius.  In  June  1902,  there  was  slight  chorea.  In 
September  another  nodule  appeared  at  the  lower  end  of  the 
left  radius.  In  January  1903,  further  nodules  of  the  same 
firm,  indolent  character  appeared  over  the  right  carpus.  In 
January  1903,  they  had  all  disappeared,  and  there  was 
apparently  complete  recovery.  There  were  several  unusual 
features  about  this  case,  and  in  particular  the  failure  of  the 
knee-joints  to  respond  to  vigorous  salicylate  treatment.  Some 
will  maintain  that  this  is  a  proof  that  the  condition  was  not 
rheumatic,  a  view  we  cannot  accept,  believing  the  specific 
action  of  the  salicylates  to  be  greatly  overrated,  and  holding 
that  the  occurrence  of  chorea  is  a  more  trustworthy  test  of 
rheumatism.  The  nodules  resembled  those  that  are  sometimes 
met  with  in  the  rheumatoid  arthritis  of  adults.  This  case  is 
again  of  particular  interest  as  bearing  upon  our  conception  of 
rheumatoid  arthritis.     Some,  in  fact  most,  authorities,  draw  a 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  291 

rigid  line  between  rheumatism  and  rheumatoid  arthritis,  an 
attitude  which  we  venture  to  think  is  not  supported  either  by 
scientific  investigation  or  by  clinical  experience. 

Summary  :  Multiple  arthritis  ;  cardiac  dilatation  ;  nodules  ; 
chorea  ;  recovery. 

Case  14.  March  1902.  P.  C,  female,  aged  5  years.  After 
two  weeks  of  pains  in  the  limbs,  she  came  under  observation 
with  arthritis  of  both  knee-joints  and  rheumatic  broncho- 
pneumonia. Her  heart  was  damaged  ;  there  were  dilatation, 
early  mitral  endocarditis  and  pericarditis.  She  recovered  with 
mitral  disease  after  a  long  illness.  In  1904  there  was  another 
attack  of  rheumatism.     This  child  is  still  under  observation. 

Summary  :  Heart  disease  ;  arthritis. 

Case  15.  June  1902.  A.  T.,  female,  aged  2  years.  The 
father  and  a  maternal  uncle  had  had  rheumatic  fever,  the 
latter  dying  of  the  disease.  The  child  had  been  ill  for  three 
months  with  arthritis  and  heart  disease.  There  was  advanced 
heart  disease,  and  a  nodule  was  present  on  the  right  olecranon 
process.  This  child  had  a  very  severe  illness,  but  ultimately 
recovered  with  a  damaged  heart,  only  to  relapse  in  the  following 
August. 

Summary  :  Carditis  ;  arthritis  ;  nodules  ;  lost  sight  of. 

Case  16.  October  1902.  B.  J.,  male,  aged  4^  years.  This 
child,  living  in  a  damp  house,  was  brought  for  chorea  and  early 
mitral  endocarditis.     He  recovered  with  a  mitral  lesion. 

Summary  :  Chorea  ;  morbus  cordis  ;  recovery. 

Case  17.  January  1903.  W.  R.,  female,  aged  4T9^-  years. 
The  mother  had  had  three  attacks  of  rheumatic  fever  and  her 
heart  was  damaged.  Three  weeks  previously  the  patient  had 
a  sore  throat  followed  by  fever  and  pains  in  the  limbs.  The 
knees  and  elbows  were  swollen  and  stiff.  The  heart  was  not 
certainly  damaged.     Recovery  followed  the  use  of  salicylates. 

Summary  :  Sore  throat  ;  arthritis  ;   recovery. 

Case  18.  May  1903.  F.  C,  male,  aged  3^-  years.  She 
had  chorea,  followed  by  heart  disease,  the  illness  commencing 
fourteen  days  before  coming  under  observation.  There  were 
relapses  in  October  1904,  and  May  1905.  The  heart  showed 
permanent  mitral  damage. 

Summary  :  Chorea  ;  heart  disease  ;  partial  recovery. 

Case  19.  May  1903.  F.  H.,  male,  aged  4  years.  The 
father  had  had  rheumatic  fever  twice.     There  was  a  history 


292  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

of  arthritis  at  three  years.  The  recent  illness  had  lasted  three 
months.  There  were  arthritis,  profound  anaemia,  carditis, 
and  nodules.  Death  occurred  in  June  from  haemorrhagic 
pericarditis.  The  diplococcus  was  isolated  from  the  pericardial 
exudation. 

Summary  :  Arthritis  ;  carditis  ;  nodules  ;  anaemia  ;  death. 

Case  20.  June  1903.  E.  C,  female,  aged  4^  years.  She 
had  chorea  at  3,  arthritis  at  3^.  She  came  under  observation 
for  active  mitral  endocarditis.  The  temperature  was  raised. 
This  patient  made  a  slow  recovery  with  a  mitral  lesion. 

Summary  :  Acute  endocarditis  ;  previous  history  of  chorea 
and  arthritis  ;  recovery. 

Case  21.  June  1903.  H.T.,  female,  aged  3^ years.  Four 
weeks  previously  there  had  been  multiple  arthritis,  and  this 
was  followed  by  severe  carditis  and  chorea.  This  case  made  a 
slow  and  incomplete  recovery. 

Summary  :  Arthritis  ;  carditis  ;  chorea  ;  partial  recovery. 

Case  22.  June  1903.  P.  C,  male,  aged  41s.  years.  At 
3rfyears  there  had  been  a  previous  attack  of  rheumatic  fever. 
The  present  illness  commenced  with  multiple  arthritis,  and 
was  followed  by  severe  carditis,  which  proved  fatal  at  the  end 
of  June.  The  necropsy  showed  adherent  pericardium,  mitral 
tricuspid  and  aortic  endocarditis. 

Summary  :  Arthritis  ;  carditis  ;  death. 

Case  23.  November  1903.  H.  S.,  male,  aged  5  years. 
One  sister  had  suffered  from  rheumatic  fever.  The  patient 
had  been  ill  a  year,  first  with  sore  throat,  then  with  pains  in 
the  limbs,  anaemia,  and  shortness  of  breath.  These  latter 
symptoms  were  present  when  first  she  came  under  observation. 
Recovery  followed  with  an  organic  mitral  lesion. 

Summary  :  Anaemia  ;  heart  disease  ;  partial  recovery. 

Case  24.  February  1904.  A.  B.,  male,  aged  2T% r  years.  His 
sister  was  under  observation  with  rheumatism.  The  child  him- 
self was  brought  for  pains  in  the  limbs  and  night  terrors.  There 
was  no  definite  heart  disease.     This  case  made  a  good  recovery. 

Summary  :  Night  terrors  ;  arthritic  pains  ;  recovery. 

Case  25.  May  1904.  E.  W.,  male,  aged  3^  years.  When 
3^  years  he  had  an  attack  of  multiple  arthritis.  This  was  a 
very  fine  boy,  the  son  of  a  fireman,  and  in  this  the  second 
attack  his  heart  was  greatly  damaged.  The  parents  lived  at 
the  fire-station,  the  ground  floor  of  which  was  always  wet  and 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  293 

damp.  The  boy  had  further  attacks  in  1905,  1906,  and  1907. 
A  prominent  feature  was  the  repeated  appearance  of  a  rheu- 
matic erythema.  He  is  still  under  observation,  with  a  greatly 
damaged  heart. 

Summary  :  Arthritis  ;  erythema  ;  carditis  ;  anaemia  ;  very 
partial  recovery. 

Case  26.  February  1904.  H.  M.,  male,  aged  4^  years. 
He  had  had  chorea  for  some  weeks,  and  there  was  a  history  of 
a  previous  attack  a  year  before.  This  patient  had  general 
chorea  and  cardiac  dilatation.     He  made  a  good  recovery. 

Summary  :  Chorea  ;  cardiac  dilatation  ;  recovery. 

Case  27.  May  1904.  D.  J.,  female,  aged  3^-  years.  The 
illness  commenced  with  a  slight  sore  throat,  followed  by 
irregular  fever,  multiple  arthritis,  anaemia,  and  carditis.  Death 
occurred  in  August. 

Summary  :  Sore  throat  ;  carditis  ;  arthritis  ;  anaemia  ; 
result,  death. 

Case  28.  August  1904.  G.  O.,  male,  aged  4^- years.  The 
father  had  had  rheumatic  fever.  The  onset  of  the  illness  was 
gradual  with  pains  in  the  chest,  breathlessness,  and  syncopal 
attacks.  The  heart  was  enormous,  and  there  was  a  loud 
mitral  murmur. 

Summary  :  Carditis  ;  lost  sight  of. 

Case  29.  August  1904.  G.  S.,  female,  aged  4^-  years. 
She  was  said  to  have  had  rheumatism  at  2^  years.  The 
mother  had  rheumatism,  the  father  rheumatic  gout.  One 
brother  had  rheumatic  fever  three  times.  One  sister  had 
muscular  rheumatism.  The  patient  was  brought  very  ill  with 
arthritis,  carditis  and  anaemia,  nodules  and  chorea.  He  made 
a  very  imperfect  recovery. 

Summary  :  arthritis  ;  carditis  ;  anaemia  ;  chorea  ;  nodules  ; 
result,  partial  recovery. 

Case  30.  January  1905.  R.  B.,  female,  aged  2^-  years. 
A  history  of  seven  days  "  cold,"  followed  by  chorea  was  given. 
The  movements  were  general  and  curiously  jerking  and  exten- 
sive, with  marked  facial  involvement.  The  heart  was  dilated, 
and  there  was  a  loud  systolic  mitral  murmur.  The  child  did 
well,  but  since  that  date  has  had  several  relapses,  and  at  the 
present  time  (1907)  there  is  definite  mitral  stenosis. 

Summary  :  Chorea  ;  morbus  cordis  ;  recovery  with  mitral 
stenosis. 


294  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

Case  31.  January  1905.  W.  C,  male,  aged  4^  years. 
His  illness  had  commenced  some  months  previously  with 
"  a  sprained  ankle  and  wrist."  For  two  months  there  had 
been  chorea,  and  there  was  also  definite  cardiac  dilatation  and 
mitral  disease.  Recovery  was  uneventful,  but  with  an  organic 
mitral  lesion. 

Summary  :  Arthritis  ;  chorea  ;  heart  disease  ;  recovery. 

Case  32.  September  1904.  A.  C,  female,  aged  4  years. 
A  brother  was  under  observation  with  rheumatic  fever.  Three 
weeks'  history  of  arthritis,  anaemia,  and  shortness  of  breath 
was  given.  There  was  cardiac  dilatation  with  mitral  disease. 
Recovery  followed  with  repeated  relapses  up  to  the  present 
date  (1907).     There  was  organic  mitral  disease. 

Summary  :  Arthritis  ;  anaemia  ;  cardiac  disease  ;  imperfect 
recovery. 

Case  33.  September  1904.  W.  S.,  female,  aged  4T^  years. 
She  had  chorea  for  ten  days.  There  was  no  obvious  cardiac 
disease.     Recovery  followed. 

Summary  :   Chorea  ;   recovery. 

Case  34.  December,  1904.  L.  T.,  male,  aged  4  years. 
There  was  ten  days'  history  of  aching  pains  in  the  legs  and 
refusal  to  walk.  Fainting  attacks  were  present.  There  was 
fever  and  the  heart  was  dilated.  Later  a  mitral  lesion 
developed.     Recovery,  with  organic  heart  disease  followed. 

Summary  :  Arthritic  pains  ;  morbus  cordis  ;  recovery. 

Case  35.  March  1905.  R.  W.,  female,  aged  4T^  years. 
Six  weeks  previously  she  had  had  a  sore  throat  followed  by 
multiple  arthritis,  nodules,  and  carditis.  Death  occurred  in 
April,  when,  in  addition,  mediastinitis,  perihepatitis,  and 
perisplenitis  were  found  to  be  present. 

Summary  :  Sore  throat  ;  carditis  ;  arthritis  ;  mediastinitis  ; 
nodules  ;  perisplenitis  ;   perihepatitis  ;  result,  death. 

Case  36.  May  1905.  E.  N.,  female,  aged  3^  years.  The 
father  had  had  rheumatic  fever.  A  paternal  aunt  had  had 
fatal  rheumatic  fever.  Four  weeks  previously,  after  some  days 
of  malaise,  with  pains  in  the  feet  and  many  other  joints, 
definite  arthritis  developed  in  the  hands  and  ankles.  There 
was  much  sour  perspiration.  Later,  pericarditis,  endo- 
carditis, arthritis,  nodules,  and  anaemia  were  present,  and 
death  occurred  early  in  June.  There  was  no  post-mortem 
examination. 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  295 

Summary  :  Pericarditis  ;  endocarditis  ;  arthritis  ;  anaemia  ; 
nodules  ;  sweating  ;  result,  death. 

Case  37.  September  1905.  M.  A.,  female,  aged  4.  A  three- 
weeks'  history  of  chorea  was  followed  by  mitral  heart  disease. 

Summary  :  Chorea  ;  heart  disease  ;  recovery. 

Case  38.  November  1905.  B.  S.,  female,  aged  4IX  years. 
The  parents  had  just  gone  into  a  new  house.  Fourteen  days 
previously  she  had  complained  of  pain  in  the  head  and  "  aches  ' ' 
in  the  limbs,  together  with  a  sore  throat.  Three  days  later 
chorea  commenced.  There  were  in  addition  mitral  disease, 
fever,  and  cardiac  dilatation.  After  a  long  illness  she  recovered 
with  a  much  damaged  heart. 

Summary  :  Sore  throat  ;  arthritis  ;  chorea  ;  heart  disease  ; 
partial  recovery. 

Case  39.  January  1906.  W.  C,  male,  aged  4T3^  years. 
Three  months  previously  he  had  suffered  from  "  a  sprained 
wrist  and  ankle."  A  month  later  chorea  developed,  hemi- 
plegic  in  type  with  aphasia.  There  was  slight  dilatation  of  the 
heart  ;  a  good  recovery  followed. 

Summary  :  Arthritis  ;  chorea  ;  cardiac  dilatation  ;  good 
recovery. 

Case  40.  February  1906.  H.  F.,  male,  aged  1^  years. 
This  was  not  a  clear  case,  but  very  suggestive.  His  father  had 
suffered  from  rheumatic  fever.  The  child,  a  weakly  infant,  had 
suffered  for  two  months  from  swelling  of  the  hands.  His  heart 
was  greatly  damaged,  with  all  the  characters  of  a  mitral  lesion, 
viz.  mitral  regurgitation,  with  much  hypertrophy  and  dilatation. 
There  was  no  cyanosis  or  clubbing.     He  was  lost  sight  of. 

Summary  :  Arthritis  ;  heart  disease. 

Case  41.  June  1906.  C.  K.,  female,  i-§-  years.  A  brother 
was  under  observation  with  active  cardiac  rheumatism.  The 
child  was  taken  suddenly  ill  with  fever  and  a  stiff  neck,  but 
there  was  neither  arthritis  nor  heart  disease.  Recovery  under 
salicylate  treatment  in  seven  days. 

Summary  ?  Stiff-neck  ;  fever  ;  recovery. 

Case  42.  September  1906.  S.  P.,  female,  aged  3  years. 
The  illness  began  suddenly  with  multiple  arthritis,  high  fever, 
and  much  sweating.  The  heart  was  dilated.  A  good  recovery 
followed  under  salicylate  treatment. 

Summary  :  Arthritis  ;  cardiac  dilatation  ;  fever  ;  sweating  ; 
recovery. 


296  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

Case  43.  September  1906.  M.  YY,  female,  aged  4^  years. 
Fourteen  days  before  coming  under  observation  she  had  a  sore 
throat,  followed  by  multiple  arthritis,  general  pericarditis  and 
mitral  disease,  anaemia,  and  wasting.  Slow  and  imperfect 
recovery  followed. 

Summary  :  Sore  throat  ;  arthritis  ;  carditis  ;  anaemia  ; 
imperfect  recovery. 

Case  44.  September  1906.  E.  E.,  female,  aged  4^  years. 
The  mother  had  had  rheumatic  fever  twice.  This  child  had, 
eight  months  previously,  suffered  from  an  attack  of  rheumatic 
fever.  The  second  illness  had  commenced  three  weeks  before 
with  slight  pain  in  the  chest,  but  no  dyspnoea.  There  was 
general  pericarditis.  This  case  made  an  excellent  recovery, 
with  a  slight  mitral  lesion. 

Summary  :  Carditis  ;  recovery. 

Case  45.  October  1906.  W.  B.,  female,  aged  4^-  years. 
The  family  were  living  in  a  damp  house  in  the  north  of  London. 
The  mother  had  suffered  from  "  gout,"  the  father  from  "  rheu- 
matic fever,"  and  one  sister,  aged  eight,  from  pains  in  the 
joints.  The  patient  had  been  ailing  for  six  months.  There 
had  been  wasting,  anaemia,  and  nocturnal  pains  in  the  joints. 
Her  heart  was  much  damaged,  the  mitral  valve  incompetent, 
and  the  cavities  dilated.     This  case  was  lost  sight  of. 

Summary  :  Anaemia  ;  arthritis  ;  wasting  ;  endocarditis. 

Case  46.  November  1906.  A.  W.,  female,  aged  43%  years. 
She  had  had  three  days'  illness  with  arthritis  of  the  wrists  and 
ankles.  In  addition,  there  was  purpura  over  the  buttocks, 
legs,  and  thighs,  and  the  heart  was  dilated.  Recovery  occurred 
under  treatment  by  rest  and  salicylates.  She  was  not  seen 
again. 

Summary  :  Arthritis  ;  purpura  ;  cardiac  dilatation. 

Case  47.  January  1907.  H.  D.,  female,  aged  3  years. 
When  z\  years  this  child  had  had  an  illness,  in  which  the  knees 
and  ankles  were  swollen.  Two  months  before  coming  under 
observation  chorea  had  developed.  The  child  was  anaemic. 
The  heart  was  enlarged,  and  there  was  a  double  mitral 
murmur.  She  made  a  slow  recovery,  and  in  December  1907, 
there  was  a  slight  relapse.  Her  father  and  paternal  grand- 
father, and  two  paternal  aunts,  had  suffered  from  rheu- 
matic fever ;  her  mother  from  rheumatism.  The  house  was 
admittedly  damp,  with  water  in  the  cellars. 


ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG  297 

Summary :  Chorea ;  anaemia ;  heart  disease ;  partial 
recovery. 

Case  48.  May  1907.  L.  S.,  female,  aged  3^  years.  Two 
weeks  after  tonsillotomy  she  complained  of  pains  in  the  limbs, 
and  became  anaemic.  When  first  seen  there  was  a  nodule 
over  the  occiput,  and  the  heart  was  severely  damaged.  After 
treatment  she  recovered  with  a  mitral  lesion. 

Summary  :  Anaemia  ;  arthritis  ;  morbus  cordis  ;  nodule  ; 
partial  recovery. 

Case  49.  September  1907.  F.  A.,  female,  aged  4^-  years. 
The  family  went  into  a  damp  house  two  months  before  and 
the  father  developed  rheumatism  in  the  joints.  The  patient 
complained  of  pains  in  the  legs,  arms,  and  abdomen.  There 
was  fever,  and  she  had  an  excited  action  of  the  heart.  Later, 
a  mitral  murmur  developed. 

Summary  :  Arthritic  pains  ;  fever  ;  morbus  cordis  ;  partial 
recovery. 

Case  50.  November  1907.  H.  C,  male,  aged  4^-  years. 
He  had  chorea  for  a  fortnight.  The  movements  were  general. 
Speech  was  considerably  affected.  The  heart  was  rapid  ;  the 
first  sound  at  the  apex  was  blurred  ;  the  temperature  was 
raised.     He  is  still  under  treatment. 

Summary  :   Chorea  ;  early  heart  disease  ;  fever. 

Case  51.  December  1907.  G.  O.,  male,  aged  4^-  years, 
subject  to  sore  throats.  The  father  has  rheumatism.  One 
sister  had  rheumatic  fever.  The  patient  four  weeks  before 
complained  of  pains  in  the  left  knee.  Arthritis  of  both  knees, 
fever,  and  dilatation  of  the  heart  were  found.  The  urine 
contained  albumin.     He  is  still  under  observation. 

Summary :  Arthritis ;  fever ;  cardiac  dilatation  ;  albu- 
minuria. 

Case  52.  December  1907.  E.  S.,  male,  aged  4^-f  years. 
The  father  and  brother  have  rheumatism.  Pains  in  ankles 
and  knees  for  some  weeks,  followed  by  chorea  of  moderate 
severity  were  complained  of.  Now  there  was  definite  chorea 
and  mitral  heart  disease.     He  is  now  under  observation. 

Summary  :  Arthritis  ;  chorea  ;  morbus  cordis. 

In  this  series  the  frequency  of  the  association  of  rheumatism 
with  damp  houses  is  noteworthy,  as  also  the  strong  family 
history  of  the  disease  in  many  instances. 


298  ACUTE  RHEUMATISM  IN  THE  VERY  YOUNG 

Appendix  II 

Seventeen  cases  of  rheumatism  in  children  over  -five  years, 

in  which  there  was  a  history  of  a  previous  attack  before 

the  fifth  year 

1.  S.   A.,   female,   aged  6.     Repeated  attacks  and  severe 
cardiac  damage.     Arthritis  at  15  months. 

2.  F.  P.,  male,  aged  7.     Chorea.     Arthritis  at  2^V  years. 

3.  B.   F.,   female,  aged  10.     Severe  morbus  cordis  of  old 
standing.     Muscular  rheumatism  at  iT^  years. 

4.  C.  B.,  male,  aged  5^.     Severe  rheumatism  and  heart 
disease.     Rheumatism  at  3  years. 

5.  S.  B.,  female,  aged  6.     Purpura.     Arthritis  and  dilated 
heart.     Rheumatism  at  3  years. 

6.  L.  D.,  male,  aged  6.     Rheumatic  heart  disease.     Arthritis 
at  4  years. 

7.  L.  B.,  male,  aged  5^.     Severe  rheumatic  heart  disease. 
Rheumatism  at  4^  years. 

8.  J.  S.,  aged  6^.     Severe  rheumatic  heart  disease.     Rheu- 
matic fever  at  3  years. 

9.  J.    R.,    female,    aged   6.     Severe   heart   disease.     Acute 
rheumatism  between  4  and  5  years. 

10.  H.  K.,  male,  aged  5^§.     Fatal  rheumatic  fever.     First 
attack  at  4  years  of  age. 

11.  J.  B.,  male,  aged  7.     Morbus  cordis.     Rheumatism  at 
3  and  5  years. 

12.  L.     R.,    female,    aged    6.     Advanced    heart    disease. 
Arthritis  at  15  months. 

13.  E.    P.,    female,    aged    6.     Chorea    and    heart    disease. 
Chorea  at  4  years. 

14.  J.  W.,  male,  aged  11.     Fatal  rheumatic  fever.     Rheu- 
matic fever  at  3  years. 

15.  F.  W.,  female,  aged  8-J-.     Rheumatic  arthritis  and  heart 
disease.     First  attack  at  4  years. 

16.  C.    C,   male,    aged   9.     Rheumatic   heart    disease   and 
nodules.     Articular  rheumatism  between  4  and  5  years. 

17.  F.    C,    female,    aged   8.     Chorea   and   morbus    cordis. 
Articular  rheumatism  at  4  years. 


PAPER  NO.  XXII 

A  CONTRIBUTION  TO  THE  STUDY  OF  RHEU- 
MATISM, WITH  NOTES  ON  THE  AFTER 
HISTORY  OF  TWENTY-FIVE  CASES  OF 
"  SCARLATINAL  RHEUMATISM  " 

(Reprinted  from  the  Quarterly  Journal  of  Medicine,  October  1909) 

In  this  clinical  paper  the  histories  of  cases  of"  rheumatism  "  arising 
in  direct  association  with  scarlet  fever  have  been  traced  over  some  years, 
and  it  is  shown  that  the  examples  described  are  indistinguishable  from 
cases  of  acute  rheumatism  arising  independently  of  the  disease.  The 
explanation  is  put  forward  that  the  rheumatic  infection  invades  the 
system  in  association  with  the  "  sore  throat  "  of  the  exanthem.  The 
possibility  of  throwing  light  upon  the  problem  of  the  streptococci  by  a 
comparative  study  of  the  rheumatic  diplococcus  and  the  streptococcus 
described  by  Dr.  Mervyn  Gordon  is  commented  upon. 

Scarlatinal  rheumatism  is  of  special  interest  because  of  its 
comparative  frequency  in  this  country,  and  because  we  have 
on  one  hand  the  researches  of  Mervyn  Gordon  and  others  on 
the  streptococcus  that  occurs  in  scarlet  fever,  and  on  the 
other  the  investigations  that  have  been  made  upon  the  same 
family  of  bacteria  in  acute  rheumatism  uncomplicated  by 
scarlet  fever.  Further,  in  both  scarlet  fever  and  rheumatism 
the  importance  of  sore  throat  is  generally  recognised,  and 
lastly,  whatever  the  true  explanation  of  scarlet  fever  itself 
may  be,  we  may  reasonably  look  upon  it  as  likely  to  influence 
any  concomitant  rheumatic  infection. 

In  looking  through  the  first  volumes  of  the  post-mortem 
records  of  the  Hospital  for  Sick  Children,  Great  Ormond  Street, 
which  date  back  some  fifty  years,  it  is  interesting  to  find 
ourselves  in  the  days  when  cases  of  scarlet  fever  were  admitted 
and  were  often  extremely  virulent.  It  would  have  been  still 
more  interesting  if  cultures  had  been  made  in  those  days  from 

299 


3oo  SCARLET  FEVER  AND  RHEUMATISM 

the  fatal  cases  of  pericarditis,  for  then  a  description  of  any 
micrococcus  which  had  been  isolated  might  have  been  compared 
now  with  that  which  has  been  since  isolated  from  uncom- 
plicated rheumatic  pericarditis.  Fortunately,  the  researches 
of  Gordon  enable  us  to  get  a  clear  idea  of  the  streptococcus 
which  he  isolated  from  cases  of  severe  scarlet  fever  and  which 
has  some  points  of  close  resemblance  to  the  rheumatic 
micrococcus. 

Clinical  investigation  has  proved  the  occurrence  of  multiple 
arthritis,  chorea,  nodules,  heart  disease,  sore  throat,  purpura, 
erythemata,  and  psoriasis,  in  association  with  true  rheumatism 
and  scarlatinal  rheumatism,  and  in  this  contribution  the  after 
histories  of  25  cases  of  rheumatism  in  childhood  directly 
associated  with  scarlet  fever  have  been  traced  during  the  last 
eight  years.  These  children  have  come  for  symptoms  of 
rheumatism,  and,  so  far  as  can  be  observed  the  clinical  features 
are  identical  with  those  of  acute  rheumatism.  One  case  was 
fatal  (No.  VI)  from  pericarditis,  and  a  strepto-diplococcus  was 
isolated,  which,  working  along  the  lines  we  had  pursued  in 
other  cases,  showed  the  same  characters  as  the  diplococcus  of 
rheumatism.  It  was  minute,  strongly  acid-producing  diplo- 
coccal  in  the  fibrinous  exudation,  and  on  experiment  caused 
multiple  arthritis  and  heart  disease  in  rabbits  with  no  suppura- 
tion in  the  viscera.  The  virulence  was  soon  lost,  but  the 
growth  once  established  was  persistent  in  subculture. 

It  will  be  seen  from  the  recorded  cases  that  the  children  who 
suffered  from  rheumatism  during  scarlet  fever  were  liable  to 
relapses  in  which  multiple  arthritis  or  chorea  or  morbus  cordis 
might  light  up  again,  and  several  of  these  symptoms  might 
appear  together.  The  arthritis  was  benefited  by  salicylates, 
the  chorea  ran  the  same  tedious  course,  the  cardiac  lesions 
were  chiefly  mitral  and  showed  no  peculiarities,  except  perhaps 
a  greater  tendency  to  tachycardia. 

Scarlatinal  rheumatism  is  well  known  to  commence  either 
soon  after  the  initial  sore  throat  or,  as  these  cases  show,  in 
association  with  a  secondary  sore  throat,  and  this  reminds  us 
that  the  portal  of  entrance  of  the  rheumatic  organism  which 
has  been  the  most  certainly  proved  is  the  tonsils.  It  may  be 
mentioned  in  passing  that  among  the  many  cases  of  acute 
rheumatism  in  childhood,  recorded  in  our  hospital  notebooks, 
we  find  that  the  two  other  acute  infections  from  which  parents 


SCARLET  FEVER  AND  RHEUMATISM  301 

have  specially  dated  attacks  of  rheumatism  in  their  children 
have  been  measles  and  diphtheria,  and  both  these  are  associated 
with  sore  throats.  These  personal  investigations  have  been 
made  quite  independently  of  the  views  of  other  observers,  but 
when  they  are  compared  with  the  statements  that  have  been 
made  in  the  standard  article  on  scarlet  fever  by  Dr.  Caiger  in 
Allbutt  and  Rolleston's  ''  System  of  Medicine,"  it  is  apparent 
that  he,  writing  from  his  aspect  of  scarlatinal  rheumatism, 
approaches  towards  the  same  position  as  the  one  to  which  we 
incline.  Thus  he  writes  :  "  There  are  good  reasons  why  it 
should  be  regarded  as  pathologically  akin  to  ordinary  acute 
rheumatism,  though  differing  in  certain  respects.  It  is  very 
prone  to  arise  in  persons  who  have  been  subject  to  attacks  of 
acute  rheumatism,  although  such  subjects  are  in  the  minority. 
It  shows,  though  in  a  less  degree,  the  same  tendency  to  move 
from  joint  to  joint,  and  it  is  readily  amenable  in  most  instances 
to  the  action  of  salicylates.  On  the  other  hand,  it  is  less  severe 
than  ordinary  acute  rheumatism,  its  natural  bent  being  towards 
recovery  :  it  is  unattended  with  the  acid  perspirations  and  the 
creamy  furred  tongue  so  characteristic  of  that  condition,  and 
it  is  less  prone  to  affect  the  tissues  of  the  heart  and  pericardium. 
Moreover,  the  joints  are  more  prone  to  take  on  a  suppurative 
action  leading  to  a  condition  of  pyaemia  than  in  ordinary 
rheumatism." 

Dr.  Caiger  is  naturally  presenting  the  subject  of  scarlatinal 
rheumatism  from  a  somewhat  different  point  of  view,  for  he  is 
writing  of  scarlet  fever  irrespective  of  the  age  of  the  patients, 
and  from  observations  during  the  course  of  the  acute  attack. 
On  the  other  hand,  we  are  only  concerned  with  children  under 
12  years  of  age  who  have  recovered  from  the  scarlet  fever,  and 
we  have  seen  the  rheumatism  when  uncomplicated  by  its 
presence.  Yet  each  of  us,  in  common  with  many  others,  are 
struck  by  the  close  resemblance  of  true  and  scarlatinal  rheu- 
matism, and  we  believe  that  it  is  in  many  cases  true  acute  rheu- 
matism. Later  in  his  observations  Caiger  adds  that  scarlatinal 
rheumatism  is  far*  more  common  in  adults  than  in  children, 
and  that  the  cardiac  structures  are  rarely  involved  at  the  time, 
probably  in  less  than  three  per  cent.  These  observations,  if  it 
were  not  for  the  saving  clause  as  to  the  relative  frequency  in 
adult  life,  would  be  strong  evidence  against  the  true  rheumatic 
origin  of  scarlatinal  rheumatism.     The  saving  clause  reminds 


302  SCARLET  FEVER  AND  RHEUMATISM 

us  that  valvular  and  pericarditic  disease  are  less  frequent  in 
adult  than  in  child  life. 

Our  cases  show  clearly  enough  that  heart  disease  is  a  common 
event  in  childhood  after  scarlatinal  rheumatism.  Thus  16  out 
of  25  had  obvious  organic  valvular  disease,  and  several  of  the 
remainder  had  dilated  hearts  or  suspicious^'  feeble  first  sounds. 
Sour  sweats,  we  know,  are  not  a  feature  of  rheumatism  in 
childhood. 

We  must  next  make  a  brief  reference  to  a  discussion  on 
rheumatism  and  its  allies  in  children,  introduced  by  Sir  Thomas 
Barlow  at  the  annual  meeting  of  the  British  Medical  Association 
held  at  Liverpool  in  1883.  This  is  to  look  back  over  a  quarter 
of  a  century  !  On  the  subject  of  scarlatinal  rheumatism 
Sir  Thomas  Barlow  thus  sums  up  :  "It  seems  possible  that 
there  may  be  at  least  two  different  forms,  but  at  all  events 
with  regard  to  many  of  the  cases  occurring  during  convales- 
cence, and  with  regard  to  the  mild  relapsing  cases  occurring 
towards  the  end  of  the  first  week,  we  must  consider  that  if  not 
identical  they  are  indistinguishable  from  true  rheumatism." 
Dr.  Ashby,  in  the  discussion,  described  two  cases  in  which  pus 
was  found  in  the  joints  and  strongly  lent  to  the  pyaemic  nature 
of  this  complication.  To  quote  his  words  :  "  In  the  first  place, 
there  is  the  greater  frequency  of  occurrence  in  some  outbreaks 
than  in  others.  Secondly,  the  regularity  with  which  the  joint 
affection  supervenes  at  the  end  of  the  first  week  ;  thirdly,  the 
severity  of  the  scarlatinal  symptoms  and  the  lightness  of  the 
joint  affection  in  most  cases,  and  the  suppuration  which  took 
place  in  two  of  the  cases  ;  and  lastly,  the  absence  of  serious 
heart  affections."  We  may  well  wonder  if  to-day  we  have 
advanced  a  single  step  from  the  position  of  1883.  We  believe, 
however,  that  the  bacteriological  investigations  on  scarlet  fever 
and  acute  rheumatism  have  really  brought  us  a  little  nearer  to 
the  means  of  closer  investigation,  and  to  a  more  complete 
understanding  of  the  problem. 

The  clinical  and  pathological  facts  in  our  series  seem  to  point 
irresistibly  to  the  occurrence  of  true  acute  rheumatism  in 
scarlet  fever,  although  there  is  the  other  problem  to  be  borne 
in  mind,  the  possibility  that  there  may  also  be  a  form  of 
rheumatism  peculiar  to  scarlet  fever.  This  we  are  not  in  a 
position  to  affirm  or  deny,  but  we  feel  that  if  it  exists  it  has 
not  yet  been  clearly  delimited  from  the  true  rheumatism,  and 


SCARLET  FEVER  AND  RHEUMATISM  303 

we  must  bear  in  mind  the  possibility  of  a  modifying  influence 
on  true  rheumatism  due  to  the  scarlatinal  poisoning.  The 
bacteriological  problem  is  a  most  difficult  one,  and  it  would 
be  a  great  assistance  if  a  careful  investigation  could  be  made 
by  an  independent  observer  of  the  micrococcus  isolated  by 
Gordon  from  scarlet  fever  and  that  obtained  by  ourselves  and 
others  from  acute  rheumatism.  We  use  the  term  "inde- 
pendent -'  because  it  has  repeatedly  struck  us  that  laboratory 
investigations  on  the  streptococci  are  carried  on  by  different 
methods,  along  different  lines  and  with  different  standards  by 
the  various  workers,  and  each  one  has  a  tendency  to  lay  stress 
on  some  particular  test  or  tests  which  he  considers  more  or  less 
specific.  Dr.  Vernon  Shaw  was  able  to  prove  to  his  satisfac- 
tion by  the  tests  that  he  applied  that  the  micrococci  described 
by  Wassermann,  ourselves,  and  Walker  were  identical.  If 
some  one  working  with  virulent  streptococci  from  scarlet  fever 
of  Gordon's  type  and  virulent  streptococci  of  the  rheumatic 
type  could  make  an  unbiased  comparison  of  them,  it  seems 
probable  that  we  should  gain  another  step  in  the  study  of 
rheumatism.  That  they  are  closely  allied  the  researches  of 
Gordon,  Andrewes,  Horder,  ourselves,  Walker,  and  Beattie 
have  already  shown.  What  are  their  specific  differences  when 
studied  together  and  by  experimental  methods,  and  the  value 
of  these  specific  differences,  are  the  essential  points  we  require 
to  know. 


Appendix 

Twenty-five  cases  of  rheumatism  directly  associated  with 
scarlet  fever 

Case  i.  September  13, 1900.  R.  C,  female,  aged  9.  When 
6  years  old  in  1897  she  had  an  attack  of  scarlet  fever  followed 
in  the  fifth  week  by  "  rheumatism  "  (viz.  arthritis),  which  kept 
her  in  bed  for  some  weeks.  This  child  was  brought  in  1900 
for  a  first  attack  of  chorea  with  a  dilated  heart.  In  1901  she 
was  again  brought  for  chorea.  In  1902  for  pleurodynia  and 
endocarditis.  In  1904  she  had  well-marked  double  mitral 
disease. 

Summary :  "  Scarlatinal  rheumatism ' ' ;  chorea,  pleurodynia ; 
morbus  cordis  ;  relapsing  type. 


304  SCARLET  FEVER  AND  RHEUMATISM 

Case  2.  October  27,  1900.  W.  W.,  female,  aged  7T%. 
Scarlet  fever  in  December  1899.  Not  well  since,  but  subject 
to  sore  throats  and  pains  in  the  muscles.  One  sister  had  had 
rheumatic  fever,  another  "  muscular  rheumatism."  September 
1900,  severe  rheumatic  arthritis.  October  1900,  chorea,  in 
hospital  for  seventeen  weeks.  March  1901,  chronic  rheumatism 
and  chorea  still  continue  ;  evidence  of  early  mitral  stenosis 
now  apparent. 

Summary  :  Never  well  since  scarlet  fever  ;  sore  throats  ; 
arthritis  ;  chorea  ;  morbus  cordis. 

Case  3.  M.  K.,  female,  aged  6.  April  15,  1902.  This 
patient  was  in  a  fever  hospital  suffering  from  scarlet  fever  and 
"  rheumatism  "  for  thirteen  weeks.  Three  days  after  leaving 
hospital  she  relapsed  with  pain  in  her  left  side  and  dyspnoea. 
She  had  never  had  rheumatism  before,  but  her  mother  had 
suffered  from  rheumatic  fever  when  twelve  years  of  age,  and 
an  elder  brother  also  suffered  from  rheumatism.  She  was 
exceedingly  anaemic  and  orthopnceic,  with  a  temperature  of 
1040  F.,  pulse  of  144  and  respiration  68  to  the  minute.  Peri- 
cardial and  pleuropericardial  friction  were  present  and  also 
extensive  endocarditis.     Death  occurred  in  seven  days. 

The  necropsy  showed  a  turbid  greenish-yellow  fluid  with 
plastic  exudation  in  the  pericardial  cavity.  Early  vegetations 
were  present  on  the  mitral  tricuspid  and  aortic  valves.  Renal 
disease  was  present,  and  a  small  white  infarct  was  also  found 
in  each  kidney.  A  minute  diplo-streptococcus,  obeying  the 
cultural  and  morphological  characters  of  the  rheumatic  diplo- 
coccus,  was  isolated  from  the  pericardial  exudation.  This  pro- 
duced arthritis,  pericarditis,  and  endocarditis  on  intravenous 
injection  into  rabbits. 

This  was  a  case  of  particular  interest  because  there  was  both 
a  definite  history  of  scarlet  fever  and  a  strong  rheumatic  family 
history.  The  micrococcus  resembled  the  rheumatic  diplococcus 
in  essential  characters,  and  the  post-mortem  evidence  showed 
a  condition  quite  indistinguishable  from  that  found  in  virulent 
rheumatism. 

Summary:  Scarlet  fever;  "rheumatism";  virulent  and 
fatal  pericarditis.  Necropsy  :  Diplo-streptococcus  in  pericar- 
dial exudate  produced  multiple  arthritis,  pericarditis,  and 
endocarditis  on  intravenous  injection  into  rabbits. 

Case  4.     E.  A.,  female,  aged  n\.     June  18,  1902.     When 


SCARLET  FEVER  AND  RHEUMATISM  305 

4  years  old  had  a  severe  attack  of  scarlet  fever,  immediately 
after  which  she  complained  of  pain  in  her  knee-joints,  but 
recovered  from  this  entirely.  The  following  year  she  again 
had  pain  in  her  knee-joints  with  effusion  which  lasted  for  six 
months.  The  effusion  appeared  first  in  the  left  knee,  then 
later  in  the  right,  and  then  again  in  the  left.  Since  this  second 
illness  she  had  never  been  well.  There  was  no  personal  history 
of  rheumatic  fever  and  no  immediate  family  history,  but  her 
maternal  grandfather  suffered  from  rheumatic  fever. 

This  child  had  great  swelling  of  both  knee-joints  with  much 
pain  and  muscular  wasting.  The  left  hip- joint  was  also 
painful.  There  was  tachycardia,  but  no  valvular  disease. 
One  enlarged  lymphatic  gland  was  felt  in  the  right  groin.  The 
spleen  was  not  enlarged.  We  explored  the  left  knee-joint, 
obtaining  a  quantity  of  clear  effusion,  containing  a  few  poly- 
morphonuclear leucocytes,  but  no  micrococci,  and  all  cultures 
were  sterile. 

Salicylate  treatment  was  ineffectual,  and  in  September  the 
condition  was  still  most  intractable,  and  although  her  general 
health  was  improved,  both  knee-joints  presented  the  appear- 
ance of  "rheumatoid  arthritis."  Most  unfortunately  we  lost 
sight  of  her  after  September  and  must  be  accordingly  content 
to  record  her  case  as  one  of  rheumatoid  type  of  obscure  nature 
following  scarlet  fever. 

Summary  :  Scarlet  fever  ;  ' '  rheumatism  ' '  ;  chronic  relaps- 
ing arthritis  of  the  rheumatoid  type  ;  tachycardia  ;  cultures 
from  arthritic  exudation  negative. 

Case  5.  A.  S.,  female,  aged  10.  November  26,  1902.  At 
five  years  of  age  was  thirteen  weeks  in  a  fever  hospital  suffering 
from  scarlet  fever  followed  by  chorea.  Three  years  later  was 
admitted  to  a  London  hospital  for  "  rheumatism  in  her  joints." 
Following  the  scarlet  fever  psoriasis  developed  and  relapses 
occurred  each  year  (five  times)  accompanied  by  pains  in  her 
limbs.  She  came  under  observation  for  a  second  attack  of 
chorea  together  %with  psoriasis.  Her  heart  was  dilated  and 
there  was  an  occasional  soft  mitral  murmur.  This  attack  of 
chorea  ran  the  usual  course. 

Summary  :  Scarlet  fever ;  chorea  (two  attacks)  ;  arthritis  ; 
psoriasis  (five  attacks). 

Case  6.  C.  W.,  female,  age  not  stated.  March  7,  1903. 
Six  months  previously  had  an  attack  of  scarlet  fever  followed 

20 


306  SCARLET  FEVER  AND  RHEUMATISM 

by  "  rheumatism."  During  the  scarlet  fever  her  throat  was 
very  inflamed.  This  child  had  recovered  from  the  arthritis, 
but  was  brought  six  months  later  for  a  severe  attack  of  chorea, 
accompanied  by  dilatation  of  the  heart  and  arthritis  pains. 

Summary:  Scarlet  fever ;  "rheumatism";  chorea;  arthritic 
pains  ;   cardiac  dilatation. 

Case  7.  W.  S.,  male,  aged  6.  October  1903.  In  June 
1903,  was  ill  for  two  months  with  scarlet  fever.  Three  weeks 
later  developed  a  sore  throat  followed  by  rheumatism  for  which 
he  was  detained  five  weeks  in  a  London  general  hospital.  In 
September,  a  week  after  leaving,  he  developed  erythema 
multiforme,  a  sore  throat,  and  shortness  of  breath.  We  found 
him  suffering  from  severe  mitral  disease  and  bronchitis,  and  so 
far  as  we  could  ascertain  this  heart  disease  showed  no  characters 
by  which  it  could  be  distinguished  from  ordinary  rheumatic 
heart  disease. 

This  case  may  be  looked  upon  as  an  example  of  acute 
rheumatism  which  chanced  to  happen  after  an  attack  of  scarlet 
fever,  but  the  sequence  of  events  is  so  close  as  to  make  it 
worthy  of  record  when  considering  the  wider  question  of 
scarlatinal  rheumatism. 

Case  8.  V.  W.,  female,  aged  6.  November  4,  1903. 
This  child  had  an  attack  of  scarlet  fever  at  two  years  (in 
1899),  and  ever  since  had  been  in  poor  health  and  suffered 
from  shortness  of  breath  owing  to  a  damaged  heart.  She 
came  under  observation  suffering  from  chorea  with  well- 
marked  mitral  disease  and  hypertrophy  of  the  heart. 
The  chorea  was  chiefly  on  the  right  side  with  much  speech 
defect.  In  January  1904  she  had  recovered  from  the 
chorea,  but  remained  in  the  same  condition  as  regards  her 
heart. 

Summary  :   Scarlet  fever  ;   morbus  cordis  ;  chorea. 

Case  9.  G.  F.,  male,  aged  10.  August  10,  1904.  Scarlet 
fever  at  the  age  of  7  and  at  that  time  arthritis  of  the  ankle- 
joints.  At  the  age  of  9  multiple  rheumatic  arthritis  with  heart 
disease.  Brought  in  1904  for  a  third  attack  of  arthritis  with 
tachycardia  and  a  cardiac  murmur.  This  boy  improved  under 
salicylate  treatment.  In  April  1905  he  again  relapsed  with 
arthritis  and  cardiac  disease. 

Summary  :  Scarlet  fever  ;  arthritis  (repeated)  ;  tachycardia  ; 
morbus  cordis. 


SCARLET  FEVER  AND  RHEUMATISM  307 

Case  10.  W.  H.,  male,  aged  10.  April  1,  1905.  Quite 
well  until  scarlet  fever  at  the  age  of  6  years  in  1901  ;  he  was 
then  in  a  fever  hospital  for  three  months  suffering  from 
"rheumatism."  On  returning  home  he  developed  chorea. 
This  boy  came  suffering  from  a  second  attack  of  chorea  with 
well-marked  mitral  disease,  the  condition  being,  so  far  as  could 
be  determined,  indistinguishable  from  the  chorea  and  morbus 
cordis  of  acute  rheumatism. 

Summary  :  Scarlet  fever  ;  arthritis  ;  chorea  (two  attacks)  ; 
morbus  cordis. 

Case  ii.  A.  A.,  female,  aged  9.  April  8,  1905.  The 
mother  of  this  child  suffered  from  chronic  rheumatism,  and  the 
patient  herself,  three  months  before  coming  under  observation, 
suffered  from  an  attack  of  multiple  arthritis  in  the  fourth 
week  of  scarlet  fever.  She  was  brought  for  rheumatism  in  the 
limbs,  dilatation  of  the  heart,  and  slight  chorea.  Her  illness 
ran  an  ordinary  course. 

Summary :  Scarlet  fever ;  arthritis ;  chorea ;  cardiac 
dilatation. 

Case  12.  M.  O.,  female,  aged  9T4?.  May  15,  1905.  This 
case  presents  the  relation  of  scarlet  fever  and  rheumatism  from 
a  somewhat  different  point  of  view.  The  patient  had  suffered 
from  rheumatic  fever  when  6  years  of  age,  and  two  years  later 
from  an  attack  of  scarlet  fever  in  which  occurred  multiple 
arthritis,  affecting  the  wrists  and  knees.  She  came  about 
eighteen  months  later  with  chorea  and  well-marked  mitral 
disease.  Her  illness  showed  no  unusual  features.  This  case, 
as  do  several  others  in  this  series,  exemplified  the  point  that 
Dr.  Caiger  emphasises  in  his  article  on  scarlet  fever  in 
Allbutt  and  Rolleston's  "  System  of  Medicine,"  i.e.,  the  occur- 
rence of  scarlatinal  rheumatism  in  those  who  are  rheumatic  in 
constitution. 

■    Summary :    Acute   rheumatism  ;     later   scarlet   fever   and 
arthritis  ;  later  chorea  and  morbus  cordis. 

Case  13.  W.  H.,  male,  aged  10.  June  17,  1905.  Four 
years  before  coming  under  observation  in  1901,  he  had  an 
attack  of  scarlet  fever  followed  at  once  by  chorea.  There  was 
no  family  history  of  rheumatism.  This  boy  had  come  to  the 
hospital  for  an  attack  of  rheumatism  of  three  months'  duration, 
commencing  with  arthritis  and  chorea.  He  had  well-marked 
mitral  disease  with  considerable  dilatation.     The  condition  was 


308  SCARLET  FEVER  AND  RHEUMATISM 

characteristic  of  ordinary  acute  rheumatism  and  recovered  in 
the  usual  imperfect  manner.  In  November  1906  he  suffered 
from  epistaxis  and  again  came  back  with  a  dilated  heart, 
cedema,  and  severe  mitral  disease. 

Summary  :  Scarlet  fever  ;  chorea  (two  attacks)  ;  arthritis  ; 
morbus  cordis. 

Case  14.  F.  S.,  female,  aged  ir£.  October  28,  1905. 
Three  years  before  (in  1902)  she  had  an  attack  of  scarlet  fever 
followed  by  chorea  three  months  later.  During  the  scarlet 
fever  there  was  "  rheumatism  "  in  the  joints.  A  year  later 
there  was  a  second  attack  of  chorea.  This  patient  came  with 
a  history  of  pains  in  the  ankles  and  knees  of  14  days'  duration 
with  mitral  disease  and  violent  chorea  which  ran  a  protracted 
course. 

Summary :  Scarlet  fever  ;  arthritis  ;  chorea  (three  attacks)  ; 
morbus  cordis. 

Case  15.  K.  R.,  female,  aged  y^.  February  1906.  This 
case  is  of  interest  for  its  bearing  upon  the  rheumatism  of 
scarlet  fever.  Her  sister  was  suffering  from  rheumatic  heart 
disease  and  chorea.  The  child  herself  had  suffered  from 
scarlet  fever  with  severe  angina,  and  had  left  the  hospital  three 
weeks.  During  those  three  weeks  she  was  noticed  to  be 
exceedingly  nervous  and  could  not  be  left  alone  at  night.  She 
also  complained  of  headaches.  Then  she  became  fidgety  and 
came  to  the  hospital  with  obvious  chorea  and  cardiac  dilata- 
tion. The  chorea  became  severe,  but  she  eventually  recovered 
with  apparently  no  permanent  cardiac  lesion.  In  January 
1908  she  again  came  with  a  relapse  of  chorea  associated  with 
a  sore  throat. 

Summary :  Scarlet  fever  ;  chorea  (two  attacks)  ;  cardiac 
dilatation. 

Case  16.  M.  W.,  female,  aged  6.  October  27,  1905.  This 
case  again  illustrates  the  close  association  of  acute  rheumatism 
and  scarlet  fever.  The  mother  of  the  child  suffered  from 
"  rheumatism  "  and  the  patient  in  April  1908  was  nine 
weeks  in  a  fever  hospital  suffering  from  scarlet  fever,  during 
which  illness  she  developed  multiple  arthritis.  Immediately 
on  her  return  home  she  developed  chorea.  The  patient 
came  for  shortness  of  breath  and  pain  in  the  chest,  and  had 
a  characteristic  early  mitral  lesion. 

Summary  :  Scarlet  fever  ;  arthritis  ;  chorea;  morbus  cordis. 


SCARLET  FEVER  AND  RHEUMATISM  309 

Case  17.  B.  C,  male,  aged  7.  November  10,  1906.  Two 
years  before  had  an  attack  of  scarlet  fever  with  nephritis,  and 
heart  disease.  He  came  suffering  from  a  double  mitral  lesion 
with  general  cardiac  enlargement  and  no  renal  affection. 

It  is  not  unreasonable  to  suggest  the  cardiac  lesion  was 
rheumatic,  and  possibly  also  the  nephritis.  It  can  be  safely 
asserted  that  the  condition  of  the  heart  did  not  resemble  that 
which  we  usually  recognise  as  a  sequela  of  chronic  renal 
disease  in  childhood.  The  high  pulse  tension,  slightly  thickened 
vessels,  and  hypertrophied  left  ventricle  of  such  cases  were  not 
present,  but  there  was  a  condition  resembling  the  usual  double 
mitral  disease  of  acute  rheumatism. 

Summary  :  Scarlet  fever  ;  mitral  disease  ;  nephritis. 

Case  18.  L.  M.,  female,  aged  8.  June  12,  1907.  The 
mother  of  the  patient  had  suffered  from  rheumatic  fever.  The 
child  herself  had  an  attack  of  scarlet  fever  in  February  1907, 
and  at  the  end  of  March  developed  chorea,  for  which  she  came 
to  the  hospital.  Her  recovery  was  good  and  without  an 
apparent  cardiac  lesion. 

Summary  :  Scarlet  fever  ;  chorea. 

Case  19.  E.  N.,  aged  7.  February  22,  1908.  When 
five  years  old  had  an  attack  of  scarlet  fever  with  nephritis  and 
arthritis  in  the  hands.  Since  that  time  has  had  rheumatic 
pains.  Brought  with  morbus  cordis.  The  heart  was  enlarged  ; 
there  was  a  systolic  mitral  and  a  slight  presystolic  murmur. 

Summary :  Scarlet  fever ;  arthritis ;  nephritis ;  morbus  cordis. 

Case  20.  G.  B.,  male,  aged  io]-|.  April  1908.  The 
maternal  uncle  of  the  patient  had  suffered  from  rheumatic 
fever;  his  mother  from  "rheumatics."  This  child  had  an 
attack  of  scarlet  fever  in  September  1907,  and  had  a  relapse 
of  sore  throat  followed  by  rheumatism  in  the  joints ;  hands, 
wrists,  and  elbows  being  affected.  In  November,  after  recovery 
from  the  "rheumatism,"  he  developed  chorea.  Brought 
April  10,  1908,  for  a  relapse  of  chorea. 

Summary  :  Scarlet  fever  ;  arthritis  ;  chorea  (two  attacks) . 

Case  21.  L.  T.,  female,  aged  10.  April  15,  1908.  Some 
years  previously  had  an  attack  of  scarlet  fever,  followed  at 
once  by  rheumatism  in  the  joints.  Since  that  time  short  of 
breath  and  subject  to  fainting  attacks.  This  case  was  of 
interest,  because  there  was  persistent  tachycardia  (pulse  120), 
some  general  enlargement  of  the  heart,  and  a  faint  mitral 


310  SCARLET  FEVER  AND  RHEUMATISM 

murmur.  The  urine  was  not  albuminous.  It  appeared  to  be 
a  case  in  which  myocardial  disease  was  the  prominent  feature, 
and  the  balance  of  evidence  favoured  the  view  that  it  was 
rheumatic  in  nature. 

Summary  :  Scarlet  fever  ;   arthritis  ;  morbus  cordis. 

Case  22.  W.  P.,  male,  aged  6|.  August  8,  1908.  Scarlet 
fever  a  month  ago.  Brought  for  a  sore  throat.  Anaemia  ; 
abdominal  pain  and  pains  in  the  wrist.  Examination  showed 
active  heart  disease  with  a  temperature  of  101.40.  This  case 
ran  a  very  severe  protracted  course,  lying  for  many  weeks  in 
the  hospital  with  active  heart  disease.  In  December  1908, 
shortly  after  leaving  the  convalescent  home,  he  returned  very 
ill  with  a  greatly  damaged  heart,  rheumatic  nodules  over  both 
elbows,  and  vague  muscular  and  articular  pains. 

This  case  can  perhaps  hardly  be  claimed  as  an  example  ol 
"scarlatinal  rheumatism,"  but  rather  as  one  of  malignant 
rheumatism  following  scarlet  fever.  It  is  worth  recording  in 
the  series,  because  though  a  month  elapsed  after  the  scarlet 
fever  before  the  boy  was  brought,  it  is  certain  that  the  condition 
had  been  in  existence  for  some  days,  and  possibly  a  week  or 
more,  which  would  date  its  onset  very  close  to  the  fever. 

Summary  :  Scarlet  fever  ;  morbus  cordis  ;  arthritic  pains  ; 
anaemia  ;  nodules. 

Case  23.  W.  K.,  female,  aged  7.  September  19,  1908. 
Scarlet  fever  and  rheumatism  in  May  1908.  In  September  a 
return  of  the  pains  in  the  limbs  with  fever  and  sore  throat. 
Early  mitral  disease.  Her  mother  had  suffered  from  rheumatic 
fever. 

Summary:  Scarlet  fever  and  "rheumatism."  Later,  sore 
throat  ;  rheumatic  pains  ;  morbus  cordis. 

Case  24.  C.  C,  female,  aged  8.  September  19,  1908. 
This  child  had  previously  been  under  observation,  suffering 
from  rheumatic  morbus  cordis.  She  now  developed  scarlet 
fever,  and  in  October  immediately  after  the  attack  of  fever 
was  over,  she  became  choreic. 

Summary  :  Rheumatic  fever  ;  morbus  cordis  ;  scarlet  fever  ; 
chorea. 

Case  25.  C.  T.,  male,  aged  9.  November  11,  1908.  Ten 
weeks  before  coming  under  observation  had  suffered  from 
scarlet  fever,  during  which  there  were  rheumatic  pains. 
Immediately   on  leaving  he  was  noted  to  begin  twitching. 


SCARLET  FEVER  AND  RHEUMATISM  311 

There  was  obvious  chorea,  anaemia,  albuminuria,  but  no 
obvious  cardiac  murmur.    His  father  suffered  from  rheumatism . 

Summary  :   Scarlet  fever  ;   chorea  ;   albuminuria. 

An  interesting  point  becomes  apparent  from  a  study  of  this 
series,  viz.,  that  one  symptom  of  rheumatism  may  be  noted 
while  a  child  is  in  a  fever  hospital,  which  may  quiet  down 
under  treatment.  When,  however,  the  child  leaves  there 
frequently  appears  within  a  month  from  departure  another 
symptom  of  rheumatism  (chorea  in  particular),  showing  that 
the  disease  was  only  apparently  cured  in  the  fever  hospital. 
This  has  important  bearing  upon  the  ultimate  prognosis  of 
scarlatinal  rheumatism. 


PAPER  x\0.  XXIII 

A  RESEARCH  UPON  COMBINED  MITRAL  AND 
AORTIC  DISEASE  OF  RHEUMATIC  ORIGIN. 
A  CONTRIBUTION  TO  THE  STUDY  OF 
RHEUMATIC  MALIGNANT  ENDOCARDITIS 

(Repriated  from  the  Quarterly  Journal  of  Medicine,  July  1912, 
vol.  v,  No.  20) 

The  introductory  part  of  this  paper  is  concerned  with  answering 
further  criticisms  which  had  been  raised  by  various  writers,  and  in 
particular  the  one  which  holds  that  the  view  that  acute  rheumatism  is  a 
specific  disease  is  based  upon  insufficient  evidence. 

The  chief  part  of  this  contribution  is  devoted  to  the  study  of  combined 
mitral  and  aortic  disease  in  rheumatism,  with  the  object  of  demon- 
strating that  in  this  lesion  must  be  sought  the  connecting  link  bewteen 
"  simple  "  and  "  malignant  "  rheumatic  endocarditis.  If  this  view 
is  a  correct  one,  it  follows  that  the  terms  "  infective  "  and  "  non-infec- 
tive," "  simple  "  and  "  malignant,"  as  applied  to  endocarditis  are  better 
abandoned  for  the  more  accurate  one  of  "  active  " — the  nature  of  the 
infection  being  supplied  as  far  as  possible  by  the  corresponding  adjec- 
tive :  thus,  active  rheumatic,  pneumococcic,  staphylococcic,  &c,  endo- 
carditis. Particular  emphasis  is  laid  upon  the  importance  of  studying 
endocarditis  as  an  event  resulting  from  an  infection,  that  is,  studying 
it  as  a  symptom  of  disease  and  not  as  a  disease  in  itself. 

Section  I 

(a)  Object  of  the  communication.  We  return  in  this  investiga- 
tion to  the  consideration  of  the  second  statement  that  we  made 
in  our  paper  upon  the  causation  of  acute  rheumatism  published 
in  the  Lancet  in  September  1900.  This  statement  was  to  the 
effect  that  acute  rheumatism  produces  a  malignant  as  well  as  a 
simple  endocarditis. 

At  the  outset  we  would  insist  upon  the  exact  wording  of  this 
assertion  in  order  to  avoid  the  mistake  being  made  that  we 

3J2 


MITRAL  AND  AORTIC  DISEASE  313 

are  thought  to  maintain  that  rheumatism  is  the  only  cause  of 
this  condition. 

It  has  been  repeatedly  proved  that  there  are  many  causes 
of  malignant  endocarditis,  and  we  would  venture  to  make  the 
generalisation  that  any  infection  which  attacks  the  valves  of 
the  heart  may  produce  this  lesion,  and  to  express  our  belief 
that  when  an  infection  which  only-  produces  endocarditis 
exceptionally  does  happen  to  attack  the  valves  then  the 
malignant  form  of  endocarditis  is  prone  to  result. 

On  many  previous  occasions  we  have  commented  upon  the 
peculiar  attitude  that  has  been  adopted  to  rheumatism,  in 
that  it  has  been  almost  universally  taught  that  it  is  a  cause  of 
simple  or  healing  endocarditis,  but  needs  the  assistance  of  a 
secondary  infection  to  produce  the  malignant  form.  Surely 
this  is  a  curious  example  of  seeking  a  difficult  path,  when  the 
plain  and  easy  one  lies  before  us. 

In  this  paper  we  are  approaching  our  subject  from  a  some- 
what different  point  of  view  to  that  from  which  we  dealt  with 
it  in  a  former  paper  (No.  XV),  for  we  are  here  studying  a  form 
of  heart  disease  which  we  believe  every  one  must  allow  may 
be  the  result  of  the  rheumatic  infection  itself  and  not  of  any 
added  infection. 

In  the  course  of  this  communication  we  shall  quote  from 
our  former  paper  which  established  certain  facts  that  may  be 
lawfully  utilised  to  illustrate  our  present  contention,  which  is 
to  this  effect  :  That  from  a  study  of  severe  heart  disease  of 
rheumatic  origin  involving  lesions  to  two  important  valves,  we 
find  all  gradations  between  simple  and  malignant  endocarditis, 
and  additional  and  striking  proof  of  the  existence  of  a  malignant 
rheumatic  endocarditis. 

We  would  also  add  that  the  original  distinction  between 
non-infective  and  infective  as  applied  to  endocarditis  should 
not  be  allowed  to  remain  for  that  such  a  division  is  in  our 
opinion  a  survival  of  an  obsolete  pathology,  and  as  such  is  a 
hindrance  to  advance  in  the  study  of  heart  disease. 

(b)  Acute  rheumatism  a  specific  disease.  We  are  desirous  at 
this  point  of  dealing  with  a  criticism  of  our  investigations 
which  has  been  frequently  repeated,  and  has  been  recently 
made  again  at  a  meeting  of  the  Pathological  Section  of  the 
Royal  Society  of  Medicine  in  March  1912.  It  is  one  to  this 
effect,  that  we  assume  the  fact  that  there  is  a  specific  disease,  acute 


314  MITRAL  AND  AORTIC  DISEASE 

rheumatism.  It  is  impossible  for  any  but  skilful  speakers  to 
answer  such  a  criticism  as  this  in  a  short  debate,  but  we  are 
prepared  to  put  in  writing  the  reasons  for  our  contentions,  to 
which  we  firmly  adhere  and  by  the  truth  or  falsity  of  which  we 
are  prepared  to  stand  or  fall. 

The  question  is  one  the  answer  to  which  necessarily  brings 
us  in  contact  with  fundamental  conceptions  of  human  disease, 
and  we  would  urge  at  once  that  diseases  such  as  acute  rheu- 
matism are  not  and  never  will  be  conditions  that  can  be 
pigeon-holed  into  compartments  with  rigid  walls .  The  farthest 
one  can  see  clearly  concerning  such  a  problem  is  this  :  That 
certain  pathological  processes  may  produce  results  in  the 
human  body,  which,  when  they  prove  fatal,  can  be  studied 
sufficiently  thoroughly,  sufficiently  accurately,  and  sufficiently 
frequently  to  permit  the  statement  that  they  clinically  and 
pathologically  present  a  process  of  disease  unlike  any  other. 
Such  a  disease  we  hold  must  be  built  up  upon  the  study  of 
fatal  cases,  although  it  may  be  frequently  delimited  at  the 
bedside  when  not  fatal. 

It  is  not  in  our  opinion  any  scientific  objection  to  the  view 
that  we  put  forward  for  a  critic  to  quote  a  case  which  has 
been  thought  by  many  doctors  to  be  acute  rheumatism  and 
yet  has  proved  to  be  of  a  different  nature  because,  for  example, 
a  staphylococcus  has  been  isolated  and  the  patient  cured  by  a 
vaccine  !  What  scientific  weight  can  such  a  statement  as  that 
possibly  have  ?  We  should  be  the  first  to  allow  that  we  have 
made  and  shall  make  errors  in  the  clinical  diagnosis  of  acute 
rheumatism,  and  that  other  diseases  may  resemble  it  very 
closely.  We  do  not  suppose  acute  rheumatism  is  the  only 
cause  of  a  transient  polyarthritis  in  man  ;  or  that  it  is  the 
only  disease  that  produces  heart  affections,  or  even  arthritis 
and  heart  disease  combined.  Twelve  years  ago  we  were  con- 
versant with  these  cardinal  difficulties  in  the  study  of  acute 
rheumatism  which  from  time  to  time  are  presented  to  us  by 
critics  as  though  they  were  new  suggestions.  We  have,  indeed, 
ourselves  pointed  out  that  some  cases  of  infection  that  result 
from  middle-ear  disease  are  almost  impossible  to  distinguish 
from  acute  rheumatism.  Yet  no  one  would  attempt  to  study 
any  disease  by  the  uncertain  light  of  exceptional  cases,  for 
such  a  procedure  would  be  foredoomed  to  failure,  and  it  is 
essential,  we  think,  in  studying  acute  rheumatism  to  investigate 


OF  RHEUMATIC  ORIGIN  315 

the  classical  examples  of  which  in  our  Hospital  note-books 
there  are  ample  records. 

The  first  step  that  we  have  believed  essential  for  establishing 
the  specific  nature  of  this  disease  has  been  to  study  side  by 
side  post-mortem  records  and  clinical  histories  of  acute  rheu- 
matism. In  this  way  we  have  obtained  not  only  the  results  of 
our  own  experience,  but  the  independent  observations  of  many 
different  skilled  physicians  and  pathologists.  The  remarkable 
records  at  the  Hospital  for  Sick  Children,  Great  Ormond  Street, 
alone  contain  upwards  of  200  fatal  cases,  and  in  addition  to 
this  we  have  many  examples  in  older  subjects  recorded  in 
recent  years  at  St.  Mary's  Hospital  and  University  College  Hos- 
pital. Further,  we  have  investigated  microscopically  on  many 
occasions  the  important  cardinal  lesions  and  the  exudations 
of  the  disease.  Lastly,  we  have  investigated  the  bacteriology 
in  nearly  100  cases,  and  studied  the  experimental  lesions. 

The  outcome  of  these  investigations  has  been  that  we  hold 
that  there  is  decisive  evidence  from  clinical  and  pathological 
observations  of  fatal  cases  that  acute  rheumatism  is  one  of 
the  most  special  of  diseases  in  this  country — a  view  we  believe 
to  be  supported  by  nearly  every  physician  of  eminence  who 
has  studied  in  a  Children's  Hospital.  Evidence  such  as  this 
is  not  to  be  lightly  set  aside  by  the  relation  of  unusual  cases, 
or  of  cases  unsupported  by  accurate  clinical  and  post-mortem 
investigations. 

It  is  as  the  infective  agent  of  this  specific  disease  that  we 
claim  the  diplococcus,  and  would  add  that  the  statement  made 
by  critics  that  various  bacteria  have  been  isolated  from  cases 
of  rheumatism  should  carry  now  no  real  weight.  The  only 
evidence  we  hold  that  can  be  now  admitted  as  worthy  of  con- 
sideration is  that  which  brings  with  it  the  proof  that  these 
various  bacteria  have  not  only  been  isolated,  but  have  repro- 
duced the  lesions  of  the  disease,  as  has  the  diplococcus.  Those 
who  maintain  that  the  cause  of  the  disease  is  still  unknown 
should  in  all  fairness  now,  after  a  period  of  at  least  ten  years 
has  elapsed,  during  which  positive  results  have  been  obtained  by 
others,  justify  their  cause  by  some  slight  positive  contribution 
of  their  own  to  our  knowledge. 

In  a  recent  and  admirable  review  of  the  study  of  rheumatism 
during  the  last  decade  by  Sanderson,1  our  position  and  that  of 
others  who  support  our  views  has  been  described  as  becoming 


316  MITRAL  AND  AORTIC  DISEASE 

more  isolated.  Even  if  we  admit  this — which  we  do  not — we 
would  venture  to  ask  of  the  impartial  looker-on,  whether 
scientific  inquiry  is  to  be  measured  by  the  number  of  investi- 
gators or  by  the  character  of  the  results  ?  As  far  as  acute 
rheumatism  is  concerned,  with  the  increasingly  isolated  group 
of  investigators  remain  such  results  as  the  demonstration  of 
experimental  arthritis  both  acute  and  chronic,  endocarditis 
simple  and  malignant,  pericarditis,  myocarditis,  pleurisy, 
peritonitis,  pneumonia,  nodule  formations,  appendicitis,  chorei- 
form movements,  large  white  kidney,  and  infarctions — all 
obtained  by  a  micrococcus  isolated  from  the  cardinal  lesions  of 
acute  rheumatism,  and  most  of  them  previously  quite  unknown 
in  the  experience  of  pathologists  in  this  country. 

Various  Types  of  Rheumatic  Infection 

If  acute  rheumatism  is  a  specific  disease,  the  result  of  infec- 
tion with  a  diplococcus  of  the  streptococcal  group,  what  clinical 
types  of  the  disease  may  be  reasonably  expected  to  be  met 
with  ?  The  answer  to  this  question  has  important  bearing 
upon  our  investigation  of  a  hundred  cases  of  mitral  and  aortic 
disease  of  rheumatic  origin,  for  we  wish  to  show  that  this 
infection  is  not  extraordinary  in  its  behaviour  but  quite  in 
accord  with  what  may  be  reasonably  expected  of  such  a 
condition. 

Firstly,  it  may  produce  a  more  or  less  general  infection  and 
damage  many  organs.  Sometimes  it  does  this  very  acutely, 
but  more  frequently  with  a  moderate  degree  of  severity.  In 
this  group  will  be  found,  as  is  the  case  with  other  infections 
many  examples  in  childhood.  In  such,  mitral  and  aortic 
disease  is  only  one  incident,  and  there  are  in  our  list  classical 
examples  of  such  cases  which  have  proved  fatal. 

Secondly,  the  severity  of  the  infection  may  fall  on  certain 
organs,  notably  the  heart,  or  even  upon  certain  parts  of  the 
heart,  for  example  the  valves. 

These  lesions  may  heal  and  leave  scars  which  in  the  case  of 
valvular  lesions  may  introduce  a  new  train  of  symptoms  the 
result  of  mechanical  heart  disease.  In  our  list  there  are 
convincing  examples  of  this  occurrence. 

Again,  the  lesions  may  heal,  or  rather  let  us  add  appear  to 
heal,  almost  entirely  and  yet  exacerbate,  or  arise  anew  as  a 
result  of  fresh  activity, with  the  result  that  we  find  after  death, 


OF  RHEUMATIC  ORIGIN  317 

evidences  of  scarring  and  activity  combined.  Thus,  thirdly, 
the  active  lesions  in  the  valves  in  such  cases  may  be  only 
incidents  in  a  renewed  general  infection,  or,  fourthly,  they 
may,  as  we  shall  hope  to  show,  be  the  cause  of  death  by  a 
virulence  and  activity  which  are  recognised  under  the  name  of 
malignant  endocarditis. 

Fifthly,  from  the  first  the  endocardial  lesions  may  show  this 
malignancy  and  be  the  cause  of  death. 

Such  various  results  of  infection  as  these  are  in  no  way 
remarkable  ;  indeed,  as  we  have  previously  stated,  it  would 
be  much  more  remarkable  if  they  did  not  occur. 

Sixthly,  it  is  only  to  be  expected  that  in  a  long  series  of  cases 
of  mitral  and  aortic  disease  examples  wall  occur  which  are 
exceedingly  difficult  to  group. 

The  result  is  wre  arrive  at  the  conclusion  that  as  a  consequence 
of  the  rheumatic  infection  we  may  find  every  grade,  from  a 
primary  malignant  endocarditis  to  long  healed  lesions,  which 
have  caused  death,  not  from  any  active  process  but  entirely 
from  a  mechanical  disability  of  the  circulatory  apparatus,  the 
result  of  the  scarred  and  deformed  valves. 

Necessity  for  considering  Mitral  and  Aortic  Disease  in 

Rheumatism  as  an  Event  in  the  History  of  an  Infective 

Process 

There  are  few  physicians  who  have  not  been  struck  with 
the  paralysing  effect  of  nomenclature  in  the  study  of  disease. 
We  have  here,  we  think,  a  very  good  example  of  such  an 
occurrence.  In  looking  through  records  it  is  brought  home  to 
us  that  a  condition  such  as  combined  mitral  and  aortic  disease 
of  rheumatic  origin  is  repeatedly  looked  upon  as  an  example 
of  "  heart  disease."  We  must  emphasise  that  for  our  purpose 
such  a  conception  is  practically  useless,  and  moreover  it  is 
frequently  not  correct.  The  condition  is  undoubtedly  in  a 
sense  one  of  heart  disease,  and  when  these  lesions  represent 
the  scars  of  some  long  dead  infection  such  a  description  is 
correct,  but  when,  as  reference  to  our  list  of  cases  will  at  once 
make  clear,  there  are  not  only  valvular  lesions  but  active 
valvular  disease,  the  condition  is  not  one  of  heart  disease  but 
of  active  heart  disease  ;  that  is,  it  is  a  phase  in  the  life-history 
of  a  prolonged  infective  process.  Our  paper  rests  in  great  part 
on  this  study  of  these  valvular  lesions  as  active  events  in  acute 


318  MITRAL  AND  AORTIC  DISEASE 

rheumatism,  and  we  shall  endeavour  to  place  them  in  the 
picture  of  a  rheumatic  infection,  and  not  to  isolate  them  under 
the  benumbing  title  of  "  heart  disease." 

The  combined  lesion  can  be  produced  experimentally  both 
as  the  result  of  a  single  and  of  a  repeated  infection,  and  in  some 
instances  the  involvement  of  the  two  valves  has  appeared  to 
be  the  result  of  a  direct  spread  of  the  infection  from  one  valve 
to  the  other,  the  segments  being  in  very  close  proximity  (see 
frontispiece).  The  usual  sequence  on  account  of  the  greater 
frequency  of  mitral  disease  is  for  the  aortic  valve  to  be  affected 
the  later  of  the  two,  but  we  would  not  deny  the  possibility  of 
the  reverse  occurrence,  although  up  to  the  present  we  have  had 
no  experimental  proof  in  its  support. 

At  the  bedside  also  we  find  the  two  lesions  appearing  in 
various  ways.  Sometimes  the  aortic  disease  follows  rapidly 
upon  the  mitral  during  a  prolonged  attack  of  endocarditis. 
Sometimes  after  a  pause  in  the  activity  of  the  infection,  but 
before  the  patient  is  well  enough  to  leave  bed,  there  is  a  definite 
recrudescence  with  the  appearance  of  an  aortic  lesion.  Again, 
aortic  disease  may  arise  in  a  subsequent  attack,  and  then  it  is 
very  difficult  to  decide  whether  it  is  an  independent  infection 
of  the  valve  by  rheumatism  or  whether  it  is  that  this  lesion  is 
recognised  by  the  appearance  of  new  clinical  signs,  but  its 
origin  in  reality  a  spread  from  the  older  mitral  endocarditis 
which  has  simultaneously  reawakened  to  activity.  Lastly,  the 
aortic  lesion  may  be  the  first  event,  although  this  is  a  less 
frequent  occurrence. 

The  combination  of  valvular  disease  is  of  interest  because  it 
shows  that  in  the  young  mitral  regurgitation  due  to  relative 
incompetence  of  an  undamaged  valve  is  decidedly  rare  as  a 
result  of  aortic  regurgitation,  for  in  such  cases  there  is  almost 
invariably  active  disease  of  the  mitral  valve  also.  It  is, 
however,  of  far  greater  interest  because  it  suggests  the  dawning 
of  a  malignant  tendency  in  the  endocarditis.  We  believe  also 
that  in  man,  as  in  animals,  there  may  be  a  direct  spread  of 
infection  from  one  valve  to  the  other,  and  that  when  this  is 
the  case  we  have  one  of  the  great  features  of  the  malignant 
type.  In  the  post-mortem  records  of  malignant  endocarditis 
emphasis  is  invariably  laid  upon  the  spread  of  vegetations  to 
the  heart  wall,  to  the  chordae  tendineae,  to  the  musculi 
papillares,  or  the  wall  of  the  aorta.     A  direct  spread  from  one 


OF  RHEUMATIC  ORIGIN  319 

valve  to  another  in  immediate  proximity  in  no  way  differs 
from  these  occurrences. 

The  clinical  study  of  rheumatic  mitral  and  aortic  disease 
illustrates  well  that  behaviour  of  the  rheumatic  infection  in 
the  tissues  which  we  have  already  foreshadowed. 

Thus,  firstly,  the  valvular  lesions  may  be  but  one  incident  in 
a  fatal  general  infection,  as  for  example  in  the  case  of  a  boy 
aged  <\\  years,  who  died  in  a  first  attack  of  acute  rheumatism 
after  twelve  weeks'  illness.  During  life  there  were  poly- 
arthritis, nodules,  and  aortic  and  mitral  disease  with  peri- 
carditis. After  death,  subacute  pericarditis  was  demonstrated 
with  acute  mitral  and  aortic  endocarditis.  In  such  cases  we 
are  dealing  with  acute  rheumatism  invading  many  tissues. 

Secondly,  the  endocardial  lesions  may  completely  heal  and 
the  patient  die  of  cardiac  disabilities  (asystole),  aortic  or  mitral 
in  type,  in  accord  with  the  predominance  of  the  particular 
lesion. 

Thus,  for  example,  a  man  aged  42,  who  had  suffered 
repeatedly  from  acute  rheumatism,  came  under  observation 
for  mitral  and  aortic  disease  with  dyspnoea  and  repeated 
attacks  of  angina  pectoris.  There  was  no  fever  and  death  was 
sudden.  The  necropsy  showed  thickened  aortic  and  mitral 
valves  with  atheroma  of  the  aorta.  There  was  no  active 
disease,  and  the  course  of  the  case  was  aortic  in  character. 

Again,  a  man  aged  50,  who  had  suffered  from  acute  rheu- 
matism at  8,  25,  36,  and  49  years,  had  been  failing  for  many 
weeks  with  progressive  dyspnoea,  dropsy,  and  the  other  signs 
of  mitral  asystole.  There  was  aortic  and  mitral  disease  and 
death  ensued.  The  necropsy  showed  mitral  stenosis  with 
shortening  of  the  chordae  tendineae,  and  calcification  of  both 
mitral  and  aortic  valves,  proof  of  a  dead  infection.  The  last 
illness  had  been  afebrile. 

Thirdly,  death  may  occur  in  a  recurrent  attack  of  a  more  or 
less  general  rheumatic  infection  in  which  once  more  the  valvular 
lesions  are  but  an  incident,  but  in  which  after  death  both 
recent  and  old  injuries  are  demonstrable. 

Thus,  for  example,  a  boy  aged  10  years,  who  had  suffered 
from  acute  rheumatism  at  6,  had  been  ill  for  twelve  weeks 
before  death.  During  this  last  illness  there  had  been  peri- 
carditis, arthritis,  and  nodules,  and  there  was  also  aortic  and 
mitral  disease.     The  necropsy  showed  recent  pericarditis  and 


320  MITRAL  AND  AORTIC  DISEASE 

thickened  aortic  and  mitral  valves  with,  in  addition,  recent 
vegetations. 

Fourthly,  the  disease  of  the  valves  may  in  a  subsequent 
attack  become  the  salient  feature  of  the  illness  and  show  that 
persistence  and  virulence  which  is  described  as  malignant. 
Thus,  a  boy  aged  13  years,  who  had  acute  rheumatism  with 
severe  carditis  at  10,  was  under  observation  for  twenty-four 
weeks  with  pericarditis  which  subsided,  and  aortic  and  mitral 
disease  which  steadily  progressed,  accompanied  by  high  fever 
and  embolisms.  The  necropsy  showed  a  recently  adherent 
pericardium  and  malignant  endocarditis  of  both  aortic  and 
mitral  valves. 

Fifthly,  from  the  first  valvular  disease  may  be  malignant  in 
type,  as  in  the  case  of  a  boy  aged  7  years,  whose  sister  and 
mother  were  the  subjects  of  acute  rheumatism,  and  who 
himself  in  an  illness  of  four  weeks  developed  first  a  polyarthritis, 
then  a  rheumatic  erythema,  and  then  pericarditis.  The 
necropsy  showed  recent  pericarditis,  malignant  mitral  and 
simple  aortic  endocarditis. 

Sixthly  and  lastly,  every  sort  of  transitional  case  may  occur, 
of  which  we  will  give  three  examples  : 

Case  i.  A  boy  aged  16  years,  who  had  suffered  from  attacks 
of  acute  rheumatism  at  6,  8,  10,  and  12  years,  was  under 
observation  in  his  final  illness  of  eight  weeks.  During  this 
period  he  developed  a  polyarthritis  which  subsided,  and  the 
combined  valvular  lesion  with  which  he  was  already  crippled 
steadily  progressed  with  high  fever  and  embolisms.  During 
life,  and  after  death,  the  case  was  described  as  a  malignant 
endocarditis,  but  the  vegetations  upon  the  aortic  and  mitral 
valves  were  pointed  out  as  small  and  resembling  those  of 
rheumatic  endocarditis. 

Case  2.  A  man  aged  19  years  had  suffered  from  acute 
rheumatism  at  n,  14,  17,  and  18.  Since  the  last  attack  his 
health  had  been  failing  for  months,  and  a  sore  throat  had 
preceded  his  final  breakdown.  Under  observation  his  tem- 
perature never  rose  above  99. 50  F.,  and  when  sudden  death 
occurred  the  natural  diagnosis  was  "heart  disease."  The 
post-mortem  examinations  showed  a  calcified  mass  on  the 
aortic  valve  with  malignant  vegetations  around  it,  and 
malignant  endocarditis  of  the  mitral  valve. 

Case  3.     The  third  case  is  a  clinical  example  only.     A  male 


OF  RHEUMATIC  ORIGIN  321 

aged  38,  who  had  previously  suffered  from  three  attacks  of 
acute  rheumatism,  was  under  observation  with  the  combined 
valvular  lesion  and  cerebral  embolism.  For  six  weeks  there 
was  persistent  fever  with  gradual  asystole,  but  eventually  there 
followed  a  slow  and  partial  recovery,  the  temperature  quieting 
down  and  the  signs  of  hemiplegia  improving.  Such  a  case 
would  be  difficult  to  place  with  any  confidence  either  as  a 
simple  or  a  malignant  type  of  endocarditis. 

This  brief  outline  of  salient  examples  brings  us  to"7  the  end 
of  the  introductory  division  of  this  paper,  for  we  know  that 
there  will  be  no  dispute  as  to  the  nature  of  the  first  three  types 
we  have  exemplified,  but  that  over  the  last  three  classes, 
namely  the  malignant  cases  supervening  on  old  rheumatic 
endocarditis,  the  primarily  malignant  ones,  and  the  transi- 
tional cases,  there  will  be  dissension  of  opinion,^ and  it  is 
these  cases  that  bring  to  a  focus  the  main  issue  of  this 
contribution. 

In  the  next  section  we  shall  frequently  use  the  term  malignant 
rheumatic  endocarditis,  but  we  do  not  use  it,  as  has  been 
asserted  ought  to  be  done,  as  connoting  rheumatism  compli- 
cated by  streptococcal  or  other  infections  of  the  endocardium. 
It  has  been  said  that  the  name  is  only  "  permissible  "  in  that 
sense  ;  we  would,  however,  modify  this  statement,  and  we 
would  claim  that  the  name  -malignant  rheumatic  endocarditis 
is  only  permissible  when  it  is  used  to  express  the  fact  that  the 
diplococcal  rheumatic  infection  may  produce  a  malignant 
endocarditis. 

Section  II 

I.  The  Establishment  of  a  Working  Basis  for  the  Thesis 

It  appears  to  us  that  the  most  simple  and  direct  method  of 
presenting  our  facts  is  to  give  first  of  all  examples  of  rheu- 
matism with  mitral  and  aortic  disease  which  we  hold  to 
establish  the  following  claims  :  (1)  That  acute  rheumatism 
may  cause  aortic  and  mitral  endocarditis.  (2)  That  this  endo- 
carditis may  eventually  prove  malignant,  although  coincident 
with  the  appearance  of  this  malignancy  other  non-malignant 
or  simple  manifestations  of  acute  rheumatism  may  appear  and 
quiet  down.  (3)  That  the  endocarditis  in  these  malignant 
cases  is  caused  by  a  strepto-diplococcus  indistinguishable  from 
that  obtained  from  simple  rheumatic  endocarditis.     (4)  That 

21 


322  MITRAL  AND  AORTIC  DISEASE 

this  strepto-diplococcus  will  produce  in  animals  on  intravenous 
injection  both  simple  carditis  and  malignant  endocarditis. 

Case  i.  A  boy,  aged  10  years,  was  admitted  suffering  from 
active  heart  disease.  Twelve  months  before  he  had  had  a 
severe  attack  of  acute  rheumatism,  during  which  both  the 
mitral  and  aortic  valves  were  damaged.  His  final  illness  had 
commenced  six  weeks  before,  with  breathlessness,  anaemia,  and 
wasting,  and  shortly  after  admission  pericarditis  developed. 
Two  weeks  later  arthritis  of  the  ankles  and  knees  appeared. 
There  seemed  very  good  reason  to  look  upon  this  condition  as 
the  result  of  another  attack  of  severe  rheumatism,  a  view 
favoured  by  the  disappearance  of  the  pericarditis  and  arthritis. 
In  spite,  however,  of  these  signs  of  improvement  the  tempera- 
ture remained  high  and  the  child  lost  ground.  The  explanation 
that  now  seemed  feasible  was  that  there  was  an  unusually 
intractable  simple  endocarditis  in  progress,  but  during  the 
next  two  months  infarctions,  sweating,  anaemia,  and  fever 
pointed  to  the  condition  as  malignant.  Death  occurred  from 
sudden  heart  failure. 

The  necropsy  demonstrated  a  generally  adherent  pericardium 
of  recent  date,  the  subsidence  of  all  arthritis,  extensive 
malignant  endocarditis  of  the  aortic  and  mitral  valves,  and 
renal  and  splenic  infarctions. 

A  pure  growth  of  strepto-diplococci  was  obtained  from  the 
valves,  indistinguishable  from  that  we  have  isolated  from 
simple  rheumatism.  The  first  rabbit  intravenously  injected 
developed  polyarthritis  and  malignant  endocarditis  of  the 
aortic  and  mitral  valves.  The  diplococcus  was  recovered  in 
pure  culture.  The  second  developed  malignant  aortic  endo- 
carditis ;  the  third,  polyarthritis  and  simple  cardiac  dilatation  ; 
the  fourth,  malignant  mitral  endocarditis  ;  the  fifth,  general 
pericarditis  and  polyarthritis  ;   the  sixth,  polyarthritis  only. 

It  appears  to  us  that  this  case  illustrates  the  four  points  we 
have  put  forward  as  rigid  tests  of  our  contention.  We  have 
the  rheumatic  origin  of  the  lesion,  the  non-malignant  evidences 
of  active  rheumatism  during  the  final  illness,  and  the  complete 
experimental  chain  of  evidence. 

The  next  case  (Case  2)  is  not  quite  so  complete  because  of 
the  absence  of  a  multiple  arthritis  during  the  final  illness. 

Case  2.  A  boy,  aged  13  years,  had  suffered  from  severe 
rheumatic  fever  at  the  age  of  10,  leaving  him  with  mitral  and 


OF  RHEUMATIC  ORIGIN  323 

aortic  disease.  For  two  months  previous  to  his  coming  under 
observation  he  had  been  ill  with  precordial  pain,  dyspnoea, 
anaemia,  and  wasting.  He  was  evidently  suffering  from  active 
carditis,  and  succumbed  after  an  illness  of  four  months. 
Throughout  the  whole  of  this  time  there  was  irregular  fever, 
and  there  was  considerable  enlargement  of  the  spleen  with 
other  signs  of  a  progressive  endocarditis. 

The  necropsy  showed  general  and  recent  pericardial  ad- 
hesions, malignant  aortic  and  mitral  endocarditis,  and  a  large 
spleen  with  infarctions. 

A  pure  growth  of  strepto-diplococci  was  obtained.  The  first 
rabbit  injected  developed  a  mitral  murmur  for  a  while  and 
eventually  died  many  weeks  afterwards — when  no  lesion  -was 
forthcoming.  No.  2  died  of  malignant  mitral  endocarditis 
with  infarctions.  No.  3  died  with  simple  mitral  endocarditis 
and  dilatation.  No.  4  died  of  fibrinoplastic  pericarditis.  No.  5 
died  with  general  recent  adhesion  of  the  pericardium. 

II.  Histological  Support 

For  many  years  emphasis  has  been  laid  upon  the  frequency 
of  a  history  of  a  previous  attack  of  rheumatic  fever  in  cases  of 
malignant  endocarditis,  and  it  is  this  that  has  led  to  the 
suggestion  that  antecedent  damage  to  the  valves  favours  the 
development  of  the  malignant  endocarditis. 

With  this  view  we  are  in  agreement,  but  our  explanation 
differs  very  distinctly  from  that  usually  accepted.  First  of  all, 
however,  we  would  point  out  that  those  who  have  opposed  our 
views  upon  acute  rheumatism  have  strangely  neglected  to 
publish  and  show  any  microscopical  studies  of  the  valvular 
lesions  of  rheumatism  and  malignant  endocarditis  in  their 
various  phases  in  man  and  animals.  Yet  this  omission  is,  we 
think,  a  serious  defect  in  their  case,  for  in  experimental  endo- 
carditis it  is  possible  to  trace  every  step  from  the  earliest 
invasion  of  the  valvular  tissues  to  the  exuberant  malignant 
vegetation,  and*  in  human  endocarditis  to  study  nearly  every 
phase  of  simple  and  malignant  endocarditis  and  the  methods 
of  their  healing. 

If  rheumatic  endocarditis  is  not  infective  in  origin  it  is 
remarkable  that  its  lesions  are  indistinguishable  from  those  of 
an  infective  process.  If,  on  the  other  hand,  it  is  the  result  of 
some  unknown  infection  it  is  interesting  to  find  that  microscopy 


324  MITRAL  AND  AORTIC  DISEASE 

is  unable  to  distinguish  between  the  nature  of  the  results 
produced  by  this  infection  and  the  malignant  endocarditis  that 
may  occur  in  the  rheumatic. 

It  is  also  interesting  to  find  that  in  the  malignant  form 
numerous  strepto-diplococci  can  be  demonstrated  in  the 
vegetations  and  are  generally  admitted  to  be  the  cause  of  the 
lesion,  but  that  in  simple  endocarditis,  in  which  the  strepto- 
diplococci  can  also  be  demonstrated — though  in  scanty 
numbers,  for  simple  endocarditis  does  not  kill — the  causal 
nature  of  these  bacteria  is  brushed  aside.  This  is  the  more 
remarkable  when  it  is  pointed  out  that  the  experimental  lesions 
of  simple  and  malignant  endocarditis,  when  obviously  caused 
in  both  instances  by  the  diplococcus  isolated  from  the  human 
lesions,  show  the  same  variation  in  the  number  of  diplococci 
in  accord  with  their  nature,  a  point  we  demonstrated  to  the 
Pathological  Society  of  London  in  1900. 

Although  there  may  be  difficulty  in  isolating  the  diplococcus 
from  rheumatic  lesions,  a  fact  which  has  been  forced  upon  us, 
we  may  add  rather  to  our  surprise,  through  the  reports  of 
other  pathologists,  we  can  hardly  think  that  there  can  be  any 
justification  for  a  failure  to  demonstrate  diplococci  in  acute 
simple  rheumatic  endocardial  lesions.  This  is  but  a  matter  of 
accurate  technique  and  sufficient  diligence,  and  that  this  may 
not  seem  a  boast,  we  will  support  it  by  a  quotation  from  a 
recent  paper  in  Heart  by  Dr.  H.  G.  Butterfield,  Graham 
Research  Scholar  in  University  College  Hospital  Medical 
School.  This  writer,  undertaking  an  entirely  independent 
research  upon  acute  carditis  and  heart-block,  of  which  we 
were  quite  unaware,  reports  thus  on  the  mitral  valve  of  a  case 
of  classical  rheumatic  carditis  : 

"  Bacteriological  examination  showed  the  presence  of 
numerous  Gram-positive  diplococci  with  a  tendency  to  short 
chain  formation  and  in  some  cases  to  only  partial  retention 
of  the  methyl  violet  stain  used.  Some  of  these  organisms  were 
very  small,  and  in  general  they  were  smaller  than  the  ordinary 
streptococcus  pyogenes."  In  our  first  paper  on  the  ^Etiology 
of  Rheumatism  we  pointed  out  the  minute  size  of  the  strepto- 
coccus and  its  only  relative  Gram-staining  properties  in  tissues. 

We  may  add  that  since  seeing  his  sections  we  asked  him  to 
undertake  the  examination  of  another  classical  case  in  which 
Dr.   Graham  Forbes  had  isolated  the  micrococcus  from  the 


OF  RHEUMATIC  ORIGIN  325 

pericardial  exudation.  In  this  he  demonstrated  the  diplococci 
in  the  lesions  of  acute  rheumatic  pericarditis. 

Why  deny  the  causal  agency  of  these  micrococci  in  the  simple 
lesions  and  accept  it  in  the  malignant,  in  the  face  of  the  positive 
experimental  results  that  have  been  published  and  specimens 
of  which  may  be  seen  by  any  interested  person  in  the  Hunterian 
Museum  ? 

There  is,  however,  another  point  that  is  established  by 
microscopy,  which  is  that  in  the  partially  healed  lesion  of 
rheumatic  endocarditis  foci  of  necrotic  tissue  are  found  shut 
off  by  fibrous  tissue  or  by  proliferating  tissue  cells. 

These  foci  we  look  upon  as  areas  of  danger  in  which  the 
micrococci  may  long  exist  in  a  latent  state.  Further,  it  is,  we 
believe,  certain  both  from  pathological  study  and  clinical 
investigation  that  the  vegetations  often  described  in  rheu- 
matism as  recent  may  have  been  of  long  standing.  Even  in  a 
case  of  fatal  carditis  where  there  was  much  thickening  and 
fibrous  change  in  the  mitral  valve,  we  found  on  section  that 
within  the  fibrous  tissue  there  were  still  areas  of  necrotic  tissue 
present.  In  such  an  occurrence  there  is  nothing  remarkable 
when  it  is  remembered  that  sometimes  rheumatic  nodules 
may  remain  for  many  months,  and  that  a  section  through 
the  centre  of  one  of  these  will  show  necrotic  tissue  ;  and  also 
that  in  chronic  pericarditis  the  same  phenomena  can  be 
demonstrated. 

The  examination  of  malignant  vegetations  throws  very 
interesting  light  on  the  sequence  of  events.  We  need  not 
delay  by  dwelling  upon  the  well-known  fact  that  in  the  most 
active  part  of  the  vegetations  thousands  of  diplococci  will  be 
found.  The  point  of  importance  is  that  in  many  of  the  slow 
cases  there  are  well-marked  attempts  at  cure  in  the  vegetation, 
and  if  this  process  is  studied  we  find  that  the  necrotic  areas 
become  less  filled  with  clearly  staining  micrococci  and  numerous 
refringent  granules  become  visible.  These  are  soon  extremely 
difficult  to  differentiate  from  the  groundwork  in  which  they 
lie,  and  at  last  an  area  is  reached  where  it  is  difficult  to  decide 
whether  the  necrotic  tissue  does  or  does  not  contain  micro- 
cocci. The  alteration  in  the  staining  properties  of  these 
micrococci  in  rheumatic  endocarditis  is  deserving  of  close 
attention,  and  we  are  surprised  that  our  critics  have  never 
commented  upon  this  point,  which  has  such  a  close  bearing 


326  MITRAL  AND  AORTIC  DISEASE 

upon  the  presence  or  absence  of  micrococci  in  this  condition. 
Now  if  we  turn  for  a  moment  to  a  study  of  some  phenomena 
in  vitro  we  find  some  suggestive  points.  The  micrococcus  of 
rheumatism  does  not  thrive  on  agar-agar — a  fact  repeatedly 
ignored.  If,  however,  we  sow  from  this  poor  culture  on  to  a 
mixture  of  bouillon,  lactic  acid,  and  milk,  and  the  growth 
recovers  sufficiently  to  clot  the  milk,  we  find  that  on  examina- 
tion of  the  amorphous  clot  numerous  micrococci  are  beginning 
to  appear.  At  first  it  is  difficult  to  be  sure  whether  one  is 
looking  at  milk  clot  or  micrococci,  later  the  micrococci  take 
the  stain  well,  and  later  still  they  form  obvious  chains.  This 
reverse  process  is  very  suggestive  and  leads  us  to  believe  that 
the  necrotic  tissue  in  damaged  valves  may  contain  micrococci 
much  more  frequently  than  is  thought. 

Our  interpretation  of  the  tendency  for  malignant  endo- 
carditis to  occur  in  the  damaged  valves  is,  then,  that  circum- 
stances of  increased  virulence  arise  and  latent  micrococci  in  the 
valves  produce  this  change  in  the  lesion.  This  inception  of  a 
new  virulence  is  not  peculiar  to  the  rheumatic  infection. 

Even  these  results  of  microscopy  do  not  exhaust  the  valuable 
assistance  that  can  be  obtained  from  this  branch  of  inquiry, 
and  we  must  confess  to  a  slight  feeling  of  injustice  when  our 
investigations  have  been  criticised  as  being  largely  dependent 
upon  cultures  from  the  throat,  which  were  open  to  the  most 
serious  error.  Such  cultures  undoubtedly  are,  and  our  work  in 
this  direction  was  not  attempted  until  we  had  isolated  the 
micrococcus  from  all  the  important  lesions  and  studied  it  by 
experiment  in  culture  and  in  the  human  and  animal  tissues. 
The  last  points  brought  out  by  a  study  of  the  microscopy  are 
these  :  that  in  some  cases  of  very  acute  simple  rheumatic 
endocarditis,  such  as  occur,  for  example,  in  rare  cases  of  fatal 
chorea,  the  vegetations,  although  minute,  contain  within  them 
vast  numbers  of  the  micrococci.  Such  a  section  is  indis- 
tinguishable from  that  through  a  malignant  vegetation,  and 
we  have  shown  such  examples  on  more  than  one  occasion. 
Again,  it  is  not  rare  to  find  in  a  fatal  malignant  endocarditis  of 
the  aortic  and  mitral  valves  simple  vegetations  upon  one  and 
malignant  upon  the  other.  On  this  account  we  have  maintained 
that  the  essence  of  malignancy  is  not  the  size  of  the  vegetations 
but  the  number  and  relative  virulence  of  the  micrococci,  a 
statement  borne  out  by  the  undoubted  fact  to  be  recognised 


OF  RHEUMATIC  ORIGIN  327 

in  our  series,  that  a  case  which  has  been  diagnosed  as  malignant 
may  at  the  necropsy  only  show  minute  vegetations. 

III.  Support  from  Blood  Cultures 

We  must  now  turn  to  the  results  of  blood  cultures  which  are 
taken  during  life  in  cases  of  acute  rheumatism  and  malignant 
endocarditis.  These  have  in  our  opinion  been  made  responsible 
for  statements  which  appear  to  us  hardly  justified  by  facts,  for 
they  require  a  very  open-minded  consideration  of  the  patho- 
logical processes  in  acute  rheumatism.  To  us  the  actual 
results  that  are  obtained,  far  from  militating  against  the  view 
we  hold  upon  the  causation,  lend  distinct  support.  If  we 
interpret  the  reasoning  of  our  critics  aright  it  is  as  follows  : 
In  many  cases  of  malignant  endocarditis  a  streptococcus  is 
obtained  by  blood  cultures,  but  in  simple  acute  rheumatism 
the  results  are  negative,  therefore  malignant  endocarditis  in 
the  rheumatic  is  an  epiphenomenon.  We  cannot  accept  these 
premisses  or  their  interpretation.  First  let  us  ask  the  unbiased 
inquirer  to  picture  the  exact  nature  of  the  processes  in  acute 
rheumatism  and  we  will  postulate  the  original  infection  as 
tonsillar  in  origin.  There  is  at  once  a  gap  in  our  knowledge 
which  is  not  likely  to  be  easily  bridged  over,  and  that  is  any 
idea  of  the  number  of  micrococci  which  gain  access  to  the 
blood  stream.  It  is  conceivable  in  the  predisposed  that  a 
small  infection  only  is  requisite,  and  that  this  original  supply 
multiplies  in  the  local  lesions.  We  do  not  yet  know  the  number 
of  micrococci  that  are  sufficient  in  such  people  to  produce 
a  definite  lesion  ;  probably  they  are  very  few.  This,  however, 
is  clear,  that  acute  rheumatism  consists  of  a  number  of  local 
foci  of  infection  in  the  tissues,  and  is  not  a  general  septicaemia. 
Further,  there  is  great  resistance  to  the  disease,  and  the 
bacteria  are  rapidly  destroyed  in  the  blood  and  in  these  tissues. 
Now  this  being  the  case,  it  seems  to  us  exceedingly  unlikely 
that  the  withdrawal  upon  one  or  two  occasions  of  some  5-10  c.c. 
of  blood  from  the  general  circulation  is  going  to  yield  a  positive 
result.  Why  should  it  ?  If  such  an  event  were  the  rule  we 
certainly  should  need  to  recast  the  pathology  of  this  infection. 
Nevertheless  in  very  severe  and  virulent  cases  with  many  grave 
lesions  and  evidences  of  systemic  poisoning  a  positive  result 
might  be  obtained.  This  is  precisely  our  own  experience,  for 
all  the  cases  of  acute  rheumatism  in  which  we  have  succeeded 


328  MITRAL  AND  AORTIC  DISEASE 

have  been  of  that  type.  Thus,  for  example,  a  girl  aged  17,  the 
victim  of  chorea  at  12,  and  rheumatic  lever  at  15  years  of  age, 
was  seized  with  acute  illness  commencing  with  sore  throat, 
multiple  arthritis,  and  purpura.  She  was  admitted  under 
Dr.  D.  B.  Lees  for  fever,  multiple  arthritis,  severe  purpura,  and 
general  carditis,  pericardial  friction  appearing  eight  days  after 
admission.  Venesection  was  ordered  on  two  occasions,  and  on 
both  a  pure  culture  of  strepto-diplococci  was  obtained.  Three 
months  later  the  patient  had  so  far  improved  as  to  be  allowed 
on  a  couch,  but  asystole  gradually  developed  and  death  ensued. 

The  post-mortem  examination  showed  recent  pericardial 
adhesions  ;  the  mitral  aortic  and  tricuspid  valves  were  all 
thickened,  but  there  were  no  recent  vegetations,  still  less 
evidences  of  malignant  endocarditis,  recent  or  old.  The  cause 
of  death  was  myocardial  disease  from  the  severe  carditis. 

Here  is  prooi  that  during  the  acute  course  of  a  severe 
rheumatic  fever  strepto-diplococci  can  be  isolated  from  the 
circulation,  and  incidentally  conclusive  evidence  that  such  a 
result  was  not  due  to  agonal  infection.  This  result  is  one  of 
very  real  importance,  for  it  disproves  the  loose  statement  that 
is  sometimes  heard,  that  the  isolation  of  bacteria  from  the 
blood  in  active  heart  disease  is  proof  of  malignant  endocarditis. 

We  must  add,  though  it  is  perhaps  obvious,  that  to  look 
upon  a  positive  culture  of  streptococci  from  the  blood  in  a  case 
of  malignant  endocarditis  as  evidence  that  the  infection  is 
not  rheumatic  is,  in  our  opinion,  quite' unjustifiable.  The 
rheumatic  diplococcus  in  fluid  media  tends  to .  become 
streptococcal  in  character,  and  believing,  as  we  do,  in  a  rheu- 
matic malignant  endocarditis  we  should  expect  a  streptococcus 
might  be  obtained  in  such  cases. 

We  would  venture  to  add  that  the  great  ^majority  of 
investigations  in  this  country  upon  malignant  ^endocarditis 
stop  short  of  throwing  any  real  light  upon  the  essential 
point  in  dispute,  for  they  almost  always  end  either  with  the 
statement  that  a  streptococcus  was  isolated,  or  with  some 
primitive  remarks  upon  the  morphology,  which  we  look 
upon  as  valueless,  as  we  note  also  does  Beattie,  or  with  an 
attempt  at  classification  by  some  laboratory  tests  in  vitro 
which  we  and  others  cannot  accept.  What  more,  it  may  be 
fairly  asked,  would  we  demand  ?  Our  answer  is,  a  careful 
series  of  experimental  and  histological  investigations.     If  as  a 


OF  RHEUMATIC  ORIGIN  329 

result  of  these  both  malignant  endocarditis,  and  simple  rheu- 
matism result,  the  answer  can  be  given  as  nearly  as  is  possible 
in  the  present  stage  of  our  knowledge.  Experimental  proofs 
far  outweigh  in  our  opinion  tests  in  vitro. 

We  have  had  other  cases  of  acute  rheumatism  which  have 
recovered  and  from  which  we  have  isolated  the  diplococcus 
from  the  blood  stream,  but  this  one,  from  the  fact  that  there 
was  a  necropsy,  stands  out  as  a  clear  proof  of  the  nature  of  the 
illness. 

When  we  have  a  malignant  endocarditis  in  rheumatism  we 
have  an  unusual  situation  to  deal  with,  in  that  there  is  then  a 
focus  teeming  with  micrococci  actually  impinging  on  the  general 
circulation.  Under  such  circumstances  it  is  only  to  be  expected 
that  blood  culture  will  prove  to  be  positive  in  a  far  greater 
proportion  of  attempts,  and  if  such  were  not  the  case  we  should 
have  also  to  recast  our  views  upon  the  pathology  of  this 
affection.  Yet  even  in  these  circumstances,  if  the  disease  is 
of  low  virulence  and  the  blood  examination  be  made  early, 
repeated  negative  results  may  be  obtained  by  skilled  bacteri- 
ologists— an  event  which  is  again  only  to  be  expected,  but  does 
not  justify  the  assertion  that  the  case  is  not  malignant. 

It  is  clear  that  we  differ  in  one  important  respect  from  our 
critics  upon  this  question  of  biood  culture,  for  we  dispute 
the  statement  that  results  in  acute  rheumatism  are  always 
negative. 

IV.  Additional  Evidence  from  a  Study  of  the  Series  of 
a  hundred  Cases 

We  believe  now  that  we  have  reasonably  established  a  claim 
to  adopt  this  attitude  toward  cases  of  malignant  endocarditis 
which  are  associated  with  previous  acute  rheumatism  or  which 
commence  as  attacks  of  rheumatism,  viz.  that  the  onus  of  proof 
that  such  are  not  rheumatic  rests  with  those  who  deny  that 
such  a  condition  exists. 

It  must  not  be  expected  that  in  this  series  of  a  hundred 
examples  of  mitral  and  aortic  cases  from  various  sources  com- 
plete chains  of  evidence  are  to  be  forthcoming,  seeing  that  few 
physicians  look  upon  the  malignant  types  from  our  point  of  view, 
and  that  no  bacteriologist,  unless  devoting  himself  to  such  a 
special  study,  will  be  likely  to  have  made  more  than  the  routine 
investigation  of  the  blood  or  vegetations.     Then  again,  in  the 


330  .MITRAL  AND  AORTIC  DISEASE 

non-malignant  cases  the  lesions  have  often  been  considered  as 
examples  of  heart  disease  and  no  particular  stress  laid  upon 
them  as  phases  in  a  prolonged  rheumatic  infection.  Our 
evidence  must  then  be  of  necessity  fragmentary,  but  it  is 
lawful  for  us,  we  think,  to  build  up  our  thesis  upon  the  carefully 
prepared  basis  of  our  complete  investigations — that  is,  upon 
the  four  claims  set  out  at  the  beginning  of  this  section, 
strengthening  the  position  by  the  aid  of  numerous  other 
important  fragments  of  evidence. 

In  order  to  avoid  any  suspicion  that  we  are  now  trying  to 
evade  a  plain  issue,  we  will  illustrate  the  character  of  our 
evidence  by  concrete  examples  of  malignant  endocarditis. 
The  first  case  we  quote  is  for  the  purpose  of  showing  that  we 
have  weighed  our  evidence  in  every  incomplete  case. 

A  child,  aged  4  years,  had  been  ill  ten  days  with  arthritis  of 
the  shoulder,  hips,  and  wrist  joints  ;  high  fever  and  mitral 
disease.     Pneumonic  signs  developed  and  death  occurred. 

In  our  opinion,  if  we  published  such  a  case  as  this  as  an 
example  of  a  virulent  first  attack  of  rheumatism  we  should 
deserve  the  most  drastic  criticism. 

The  necropsy  showed  periostitis  of  the  right  femur,  multiple 
suppurative  arthritis,  suppurative  pericarditis,  abscesses  in  the 
muscles,  and  early  mitral  disease.  The  Staphylococcus  pyogenes 
aureus  was  isolated  and  was  the  cause  of  the  illness. 

On  the  other  hand,  a  girl  aged  11  had  an  attack  of  acute 
rheumatism  at  9  and  again  at  10  years.  Her  final  illness 
showed  active  carditis  with  persistent  fever  ;  no  infarctions 
were  observed.  A  strepto-diplococcus  was  isolated  from  the 
blood  and  at  the  necropsy  malignant  aortic  disease  was  dis- 
covered with  acute  mitral  of  the  simple  type.  Both  valves 
showed  former  disease.  The  other  viscera  accorded  with  the 
diagnosis  of  a  rheumatic  infection.  Such  a  case  we  claim  to 
be  rheumatic. 

There  is  a  very  close  clinical  and  pathological  similarity  in 
many  of  these  cases  of  malignant  endocarditis  which  becomes 
apparent  from  the  short  details  of  twenty-five  examples  that 
occurred  in  our  series,  and  we  feel  justified  in  claiming  some 
cases  upon  such  clinical  or  clinical  and  pathological  evidence, 
admitting  at  once  that  the  proof  is  not  complete,  but  believing 
the  explanation  as  by  far  the  most  probable. 

Case  i.     A  man  aged  27  years  had  chorea  as  a  boy,  and  an 


OF  RHEUMATIC  ORIGIN  331 

attack  of  rheumatic  fever  at  26.  He  never  laid  up  during  the 
attack,  but  struggled  on  with  his  work,  gradually  losing 
ground.  Compelled  at^last  to  take  to  bed,  nine  months  after  the 
neglected  illness,  he  was  found  to  have  aortic  and  mitral 
disease  with  fever  and  died  in  under  a  fortnight.  The  necropsy 
showed  malignant  aortic  and  mitral  disease  and  evidence  of 
previous  cardiac  rheumatism. 

This  case  we  would  explain  as  a  rheumatic  malignant  endo- 
carditis, probably  produced  by  neglect  of  the  acute  rheumatism, 
an  explanation  which  would  necessarily  fail  if  others  can 
produce  a  series  of  examples  of  such  cases  for  which  a  better 
solution  can  be  given.  We  think  that  in  this  case  also  the 
endocarditis  had  probably  been  active  the  entire  nine  months 
and  was  only  under  observation  in  the  terminal  phase. 

Case  2.  The  next  case,  which  is  of  interest  as  an  aortic  and 
mitral  one  that  cannot  be  included  in  our  series,  illustrates  the 
difficulties  that  have  to  be  encountered  in  any  attempt  at  the 
study  of  disease  in  man. 

A  woman,  aged  28,  had  suffered  from  rheumatic  carditis 
after  scarlet  fever  as  a  child  and  had  never  been  well  since  her 
confinement  thirteen  months  before.  At  the  time  of  her 
confinement  there  was  fever.  After  ten  weeks  of  acute  illness 
with  purpura,  paroxysmal  fever,  multiple  embolisms,  and  pro- 
gressive weakness  she  succumbed.  No  organism  was  isolated. 
The  necropsy  showed  large  vegetations,  some  with  calcareous 
deposits  in  them,  on  the  aortic  valve  and  the  anterior  flap  of 
the  mitral.  There  were  no  abscesses,  but  white  infarcts. 
Those  who  claim  that  this  was  a  secondary  infection  of  septic 
nature  dating  from  the  confinement  have  as  strong  evidence  in 
their  favour  as  those  who  would  suggest  that  there  was  a 
lurking  rheumatic  endocarditis,  which,  in  the  puerperal  state, 
awoke  to  virulence.  The  data  are  therefore  insufficient  and 
the  case  valueless  on  this  account. 

There  is  another  difficulty  to  be  faced  over  the  determination 
of  the  nature  of  a  carditis  which  is  from  the  first  malignant 
and  is  apparently  the  solitary  lesion,  or  almost  so.  No  one 
disputes  the  occurrence  of  a  primary  simple  rheumatic  endo- 
carditis, that  is,  a  pure  cardiac  rheumatism — and  we  naturally 
go  a  step  further  and  ask,  if  this  is  admitted,  why  deny  the 
possibility  of  the  same,  but  in  a  malignant  form,  occurring  in 
a  first  attack  of  rheumatism  ?     Experiment  proves  that  the 


332  MITRAL  AND  AORTIC  DISEASE 

rheumatic  organism  can  produce  malignant  endocarditis  in  a 
previously  healthy  valve. 

Example  i.  Thus,  for  example,  a  child  of  fourteen  years 
who  gave  no  history  of  previous  illness  was  seized  with  a 
sudden  hemiplegia.  There  were  irregular  fever  and  wasting 
for  seven  weeks,  and  evidence  of  mitral  disease.  Blood  culture 
was  negative.  Malignant  mitral  endocarditis  and  mitral 
disease  were  present  with  infarctions. 

This  was  not  a  mitral  and  aortic  case,  but  even  if  it  had 
been  we  should  not  have  included  it  in  our  series  for  lack  of 
data.  Nevertheless,  it  is  most  probable  that  this  was  an 
example  of  malignant  rheumatic  endocarditis. 

Example  2.  The  ground  is  far  safer  in  the  following 
example,  already  quoted  in  the  first  section,  of  a  boy  aged 
7  years,  whose  mother  and  sister  were  the  subjects  of  acute 
rheumatism,  and  who  himself  in  an  illness  of  four  weeks 
developed  polyarthritis,  a  rheumatic  erythema,  and  then  fatal 
pancarditis.  Simple  aortic  and  malignant  mitral  disease  were 
found  with  pericarditis  and  the  strepto-diplococcus  isolated. 
In  this  case  we  have  other  manifestations  of  acute  rheumatism. 
Such  a  case  we  look  upon  as  undoubtedly  rheumatic  and  as  a 
link  with  that  group  which  for  the  present  purpose  we  may 
call  transitional,  in  that  they  are  clinically  on  the  border  line 
between  simple  and  obviously  malignant  endocarditis. 

Example  3.  Again,  a  girl  of  nine  years  had  been  ill  four 
months  with  moderate  and  persistent  fever.  Polyarthritis  had 
developed  early  in  the  illness  and  passed  off  ;  then  severe 
mitral  and  aortic  disease  developed,  with  an  enlarged  spleen 
and  multiple  embolisms.  After  death,  malignant  aortic  and 
mitral  endocarditis  was  present. 

We  are  aware,  as  one  of  the  cases  we  have  chosen  has 
illustrated,  that  a  polyarthritis  in  a  child  need  not  be  rheumatic. 
A  transient  affection  of  the  joints  such  as  occurred  in  the  above 
case  is,  however,  much  more  suggestive  of  acute  rheumatism 
than  any  other  disease.  When  a  series  of  cases  of  this  kind 
is  studied  and  all  the  evidence  we  have  put  forward  deliberately 
weighed,  we  beheve  that  we  are  justified  in  asking  that  those 
who  dispute  the  nature  of  such  an  arthritis  and  endocarditis 
should  produce  definite  facts  in  support  of  their  contention, 
and  not  generalise  from  the  well-known  fact  that  there  are 
many  causes  of  arthritis. 


OF  RHEUMATIC  ORIGIN  333 

We  repeat  that  the  preceding  cases  have  been  quoted  in 
order  to  show  that  now  that  we  are  dealing  with  examples  of 
malignant  endocarditis  which  have  not  been  completely 
investigated  we  have  not  assumed  that  they  are  necessarily 
rheumatic,  but  have  balanced  the  evidence  both  for  and 
against  this  view.  The  appended  list  from  our  series  given  in 
brief  will  enable  the  reader  to  form  his  own  opinion  upon  the 
value  of  our  evidence.  We  may  add  that  from  among  the 
cases  we  searched  through,  nine  examples  of  malignant  endo- 
carditis have  been  excluded  because  they  were  obviously  the 
result  of  other  infections,  and  fifteen  were  of  uncertain  nature 
and  open  to  grave  criticism. 

It  is  very  interesting  to  find  in  the  list  below  all  grades  of 
virulence  in  the  rheumatic  process,  and  there  are  some  cases 
which  lead  us  to  the  next  group.  This  is,  we  admit,  quite  an 
artificial  one  and  called  by  us  transitional  because  it  bridges 
over  the  gap  between  the  certainly  malignant  and  the  third 
group,  which  contains  examples  of  acute  rheumatism  showing 
damage  to  the  mitral  and  aortic  valves  of  the  simple  type.  As 
we  pass  to  the  transitional  group  the  conclusive  evidence 
becomes  more  and  more  difficult  to  obtain,  because  recovery 
is  more  likely  to  occur,  and  among  these  examples  it  may  well 
have  been  that  some  were  in  reality  of  the  malignant  type  and 
others  of  the  simple.  It  is,  if  our  view  is  correct,  much  more 
scientific  to  abandon  these  two  terms  simple  and  malignant 
and  to  substitute  for  them  active  rheumatic  endocarditis.  Such 
a  term  is  much  more  satisfactory  from  every  point  of  view,  for 
it  is  less  alarming  to  the  patient  ;  it  represents  more  accurately 
the  true  pathology  and  in  no  way  blinds  our  eyes  to  the  mean- 
ing of  this  activity  when  it  reaches  the  degree  in  which  the 
embolic  phenomena  and  consequent  systemic  poisoning  show 
that  life  is  clearly  threatened.  Possibly  the  objection  may  be 
raised  that  such  a  condition  of  malignancy  is  utterly  unlike 
any  other  manifestation  in  rheumatism,  but  we  would  point 
out  that  no  other  severe  lesion  in  this  disease  could  run  a 
parallel  course,  however  malignant  it  might  be,  for  no  other 
rheumatic  lesion  stands  in  the  same  relation  to  the  general 
blood  stream. 

There  is  a  statement  that  has  been  made  about  the  relation 
of  an  attack  of  malignant  endocarditis  to  previous  rheumatic 
heart  disease  which  we  would  traverse  as  a  very  misleading 


334 


MITRAL  AND  AORTIC  DISEASE 


one.  It  is  to  the  effect  that  the  two  conditions,  though 
associated,  are  as  a  rule  quite  independent  of  one  another. 
Our  series  shows  that  there  may  be  every  variety  of  relation 
from  immediate  to  remote,  and  we  would  add  that  because  the 
relation  is  a  remote  one  it  is  no  proof  at  all  that  the  malignant 
process  is  non-rheumatic.  If  any  statement  can  be  made 
about  such  cases  it  would  be  that  the  final  condition,  other 
things  being  equal,  is  more  likely  to  be  rheumatic  than  the 
result  of  any  other  infection. 

Analysts  of  ioo  Cases  of  Rheumatic  Aortic  and  Mitral  Disease 

At  this  point  before  we  give  the  first  Table  of  cases  illustrating 
rheumatic  mitral  and  aortic  lesions,  it  will  be  convenient  to 
give  a  brief  analysis  of  the  complete  series  of  ioo. 

i.  Sex.     51  were  females  and  49  males. 


The  age  incidence  was  as  follows  : 


15  per  cent. 

32 

23 


15 

10 

3 

1 
1 


1-10  years 
11-20 
21-30 
31-40 
41-50 
51-60 
61-70 
71-80 

3.  Clinical  groups. 

I.  Cases  developing  from  the  first  or  in  subsequent  attacks 
malignant  endocarditis,  25. 

II.  Cases  on  the  border  line  between  malignant  and  simple 
endocarditis,  at  least  13. 

III.  Cases  illustrating  acute  rheumatic  simple  endocarditis, 
either  as  an  incident  in  a  widespread  infection  or  as  the  pre- 
dominant lesion,  33. 

IV.  Cases  illustrating  mechanical  disabilities  from  the  results 
of  scarred  valves  : 

A.  Symptoms  chiefly  aortic  :  6  cases. 

B.  Symptoms  chiefly  mitral  :  22  cases. 

4.  Fatal  cases. 

44  cases  were  fatal — and  some  of  the  others  who  left  the 
hospitals  were  taken  away  on  account  of  their  hopeless 
condition. 


OF  RHEUMATIC  ORIGIN  335 

23  of  the  25  examples  of  malignant  endocarditis  in  Group  I 
succumbed,  and  the  remaining  2  only  returned  home  in  a 
dying  condition. 

4  of  the  13  cases  in  Group  II  were  fatal,  but  this  group  is  an 
artificial  one,  made  for  the  purpose  of  exposition,  and  is  not 
to  be  looked  upon  as  an  entity. 

11  of  the  33  in  Group  III  were  fatal. 

6  (2  in  Group  A  and  4  in  Group  B)  were  fatal  of  the  29  cases 
in  Group  IV. 

5.  Bacteriological  evidence  is  necessarily  incomplete,  for  in 
the  majority  of  cases  none  was  made.  12  positive  results  were 
obtained  in  the  25  malignant  cases  and  6  were  reported  nega- 
tive. The  comparative  success  in  this  group  is  entirely  in 
accord  with  the  view  of  the  pathology  we  have  put  forward. 

Negative  results  in  the  simple  rheumatic  cases  (Group  III) 
are  the  rule,  but  there  are  exceptions.  We  would  repeat  that 
a  single  or  even  two  such  examinations  of  the  blood  are  but 
little  evidence  of  the  presence  or  absence  of  an  infective  process 
when  the  result  is  negative,  and  that  in  our  opinion  far  too 
much  weight  has  been  laid  upon  the  occurrence  of  these 
negative  results  when  the  morbid  processes  in  acute  rheumatism 
are  thoroughly  realised. 

6.  The  relation  of  the  final  illness,  when  fatal,  to  the  last 
attack  of  rheumatism  can  be  readily  studied  from  our  lists. 
The  facts  thus  obtained  are  only  relative,  for,  when  a  patient 
has  been  the  victim  of  repeated  attacks  of  acute  rheumatism, 
the  more  closely  the  history  is  investigated  the  more  frequently 
will  be  found  evidence  of  some  activity  of  the  rheumatic 
processes  between  the  definite  attacks  :  these  minor  attacks 
are  frequently  not  recorded  and  not  mentioned  by  the  patients. 

7.  All  the  observations  upon  the  duration  of  the  illness  are 
also  only  approximate,  but  they  serve  to  illustrate  how  pro- 
longed the  illness  may  be  and  how  difficult  it  is  to  ascertain 
the  commencement  or  the  end  of  the  active  processes. 

fc  8.  We  would  lay  special  stress  upon  the  following  histories 
from  the  groups  of  the  malignant  cases.  First,  three  in  which 
the  malignant  process  dated  from  the  first  illness  ;  two  in 
which  it  followed  upon  an  attack  of  rheumatism  six  months 
before,  from  which  illnesses  the  patients  had  never  really 
recovered  ;  one  in  which  there  was  a  continuous  history  of 
failing  health  for  twelve  months  after  the  fourth  attack  of 


336  MITRAL  AND  AORTIC  DISEASE 

acute  rheumatism  ;  one  in  which  the  patient  neglected  a 
previous  attack  of  rheumatism  which  had  occurred  less  than 
a  year  before  and  after  which  he  had  been  ill  fed  and  had  kept 
at  work  ;  one  in  which  there  had  been  failing  health  following 
a  rheumatic  polyarthritis  five  months  previously. 

These  8  cases  out  of  a  series  of  25  show  the  close  relationship 
of  the  rheumatic  process  to  malignant  endocarditis.  9  more 
illustrate  the  malignant  endocarditis  emerging  from  other 
and  transitory  symptoms  of  acute  rheumatism.  Thus  17  of 
these  25  cases  show  a  close  relationship  to  the  occurrence  of 
acute  rheumatism. 

Group  No.  I 

Mitral  and  Aortic  Cases  Malignant  in  Type 

Case  i.  M.,  aged  10.  Acute  rheumatism  at  9  years. 
Main  symptoms  of  final  illness  :  Admitted  with  mitral  and 
aortic  disease — developed  transient  polyarthritis  and  peri- 
carditis. Later  infarctions,  persistent  fever,  &c.  Approximate 
duration  :  18  weeks.  Bacteriology  :  Strepto-diplococcus  iso- 
lated from  valves.  Result  :  Death.  Malignant  mitral  and 
aortic,  recent  pericardial  adhesion,  white  infarctions  in  spleen 
and  kidneys. 

Case  2.  M.,  aged  13.  Acute  rheumatism  at  10  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease, 
transient  pericarditis.  Infarctions  and  persistent  high  fever. 
Approximate  duration  :  24  weeks.  Bacteriology  :  Strepto- 
diplococcus  isolated  from  valves.  Result  :  Death.  Malignant 
mitral  and  aortic,  recent  and  old  pericarditis,  infarctions. 

Case  3.  M.,  aged  16.  Acute  rheumatism  at  6,  8,  10,  and 
12  years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease,  transient  polyarthritis,  fever,  infarctions.  Approxi- 
mate duration  :  8  weeks.  Bacteriology  :  Strepto-diplococcus 
isolated.  Result  :  Death.  Malignant  in  the  clinical  course 
and  in  the  post-mortem  evidence  of  infarctions,  but  the 
vegetations  on  the  two  valves  resembled  those  of  severe  simple 
endocarditis. 

Case  4.  F.,  aged  37.  Acute  rheumatism  at  23  years. 
Main  symptoms  of  final  illness  :  Polyarthritis  (subsiding), 
aortic  and  mitral  disease,  enlarged  spleen,  high  fever,  progres- 
sive course.  Approximate  duration  :  18  weeks.  Bacteriology: 
Strepto-diplococcus    isolated    from    blood    stream.     Result  : 


OF  RHEUMATIC  ORIGIN  337 

Death.     Simple   aortic   endocarditis.     Malignant   mitral.     In- 
farctions in  the  spleen. 

Case  5.  M.,  aged  7.  Acute  rheumatism  :  ^First  attack. 
Main  symptoms 5 of  final  illness:;  Polyarthritis,  pericarditis, 
erythema  multiforme,  acute  aortic  and  mitral  disease,  high 
fever.  Approximate  duration  :  ,4^weeks.  Bacteriology: 
Strepto-diplococcus  from  pericardial  fluid.  Result :  Death. 
Sero-fibrinous  pericarditis,  acute  simple  aortic,  malignant  mitral 
endocarditis. 

Case  6.  F.,  aged  14.  Acute  rheumatism  at  12  and  13 
years.  Main  symptoms  of  final  illness  :  Transient  polyarthritis, 
mitral  and  aortic  disease  with  continuous  fever,  evidences  of 
infarction  and  nephritis.  Approximate  duration  :  6  weeks. 
Bacteriology  :  Negative.  Result  :  Death.  The  endocarditis 
was  in  character  of  the  simple  type  ;  the  lesions  qua  infarctions 
and  nephritis,  and  the  clinical  course,  were  of  the  malignant 
type. 

Case  7.  F.,  aged  21.  Chorea  at  7  years  ;  acute  rheumatism 
at  20  years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease  with  irregular  fever,  infarctions,  and  nephritis.  Ap- 
proximate duration  :  16  weeks.  Bacteriology  :  No  report. 
Result  :  Death.  Malignant  type  of  vegetations  on  the  mitral 
valve.     On  the  aortic  and  tricuspid  valves  small  vegetations. 

Case  8.  F.,  aged  37.  Acute  rheumatism  as  a  child  and 
6  months  before  final  illness.  Main  symptoms  of  final  illness  : 
This  illness  imperceptibly  followed  upon  an  attack  of  rheumatic 
arthritis  6  months  before.  There  were  aortic  and  mitral 
disease.  Moderate  intermittent  fever  and  infarction.  Ap- 
proximate duration  :  probably  6  months.  Bacteriology  : 
Negative.  Result  :  Death.  Malignant  endocarditis  of  the 
mitral  and  aortic  valves  with  infarctions  in  spleen. 

Case  9.  M.,  aged  19.  Acute  rheumatism  at  11,  14,  17, 
and  18  years.  Main  symptoms  of  final  illness  :  This  patient 
had  never  recovered  from  his  last  attack  of  acute  rheumatism, 
but  his  symptoms  increased  after  a  sore  throat,  being  those  of 
mitral  and  aortic  disease  with  slight  fever  never  above  99.5  °  F. 
Sudden  death  occurred  and  the  case  was  not  suspected 
to  be  malignant.  Approximate  ^duration  :  over  12  months. 
Bacteriology  :  None  made.  Result :  Death.  Malignant  mitral 
endocarditis  recent  and  some  vegetations  on  the  aortic  seg- 
ments which  were  thickened  and  calcified. 

22 


33«  MITRAL  AND  AORTIC  DISEASE 

Case  io.  M.,  aged  50.  Acute  rheumatism  at  42  years. 
Mam  symptoms  of  final  illness  :  An  illness  of  some  months' 
duration  with  transient  polyarthritis  in  the  articulations  of  the 
fingers.  Aortic  and  mitral  disease,  later  infarctions  and 
purpura.  The  pyrexia  persistent  but  at  first  mild,  gradually 
increased  in  severity.  Approximate  duration  :  Some  months. 
Bacteriology  :  Strepto-diplococcus  from  the  circulation. 
Result  :  Death.  Malignant  endocarditis  of  the  mitral,  aortic, 
and  tricuspid  valves. 

Case  ii.  F.,  aged  16.  Acute  rheumatism  at  12  years. 
Main  symptoms  of  final  illness  :  A  long  illness  with  poly- 
arthritis, persistent  fever,  aortic  and  mitral  disease,  and 
infarctions.  Approximate  duration  :  14  weeks.  Bacteriology  : 
Strepto-diplococcus  from  the  circulation.  Result  :  Death. 
No  necropsy,  but  a  case  of  the  malignant  type. 

Case  12.  F.,  aged  n.  Acute  rheumatism  at  9  and^io 
years.  Main  symptoms  of  final  illness  :  A  comparatively 
rapid  case  in  which  there  was  high  fever  and  severe  aortic  and 
mitral  disease.  Approximate  duration  :  7  weeks.  Bacterio- 
logy :  Strepto-diplococcus  isolated  from  circulation.  Result  : 
Death.  Small  vegetations  on  the  mitral,  malignant  on  the 
aortic  valve.     No  infarctions. 

Case  13.  M.,  aged  27.  Chorea  as  a  boy  ;  acute  rheu- 
matism at  26  years.  Main  symptoms  of  final  illness  :  During 
the  attack  of  acute  rheumatism  at  26  the  patient  would  not 
rest  but  persisted  with  his  work — steadily  losing  ground  with 
cardiac  symptoms  until  within  10  days  of  his  death.  During 
this  time  there  was  fever  with  severe  mitral  and  aortic  disease. 
Approximate  duration  :  About  9  months  ;  10  days'  acute 
illness.  Bacteriology :  No  record.  Result :  Death.  Malignant 
aortic  and  mitral  endocarditis. 

Case  14.  F.,  aged  16.  Acute  rheumatism  at  12  years. 
Main  symptoms  of  final  illness  :  Admitted  with  multiple 
arthritis,  which  subsided,  and  also  mitral  and  aortic  disease. 
For  some  3  months  there  was  high  fever.  The  spleen  enlarged 
and  was  tender.  Approximate  duration  :  About  12  weeks. 
Bacteriology :  No  record.  Result  :  Death.  No  post- 
mortem. 

Case  15.  M.,  aged  11.  Acute  rheumatism  at  7^  years. 
Main  symptoms  of  final  illness  :  A  case  of  progressive  mitral 
and  aortic  disease — pericarditis  with  transient  polyarthritis, 


OF  RHEUMATIC  ORIGIN  339 

infarctions,  enlarged  spleen,  and.  irregular  fever.  Approximate 
duration  :  n  weeks.  Bacteriology  :  Strepto-diplococcus  from 
bloodstream.  Result :  Death.  Recent  pericarditis.  Malignant 
mitral  and  small  aortic  vegetations. 

Case  16.  M.,  aged  13.  Acute  rheumatism  at  7  years. 
Main  symptoms  of  final  illness  :  A  case  of  progressive  mitral 
and  aortic  disease  with  irregular  fever  and  infarctions.  Ap- 
proximate duration  :  17  weeks.  Bacteriology  :  Negative. 
Result  :  Death.  Aortic  malignant  vegetations,  mitral  small 
vegetations. 

Case  17.  F.,  aged  9.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Admitted  with  multiple 
arthritis  and  mitral  and  aortic  disease  ;  there  was  moderate 
irregular  fever  throughout.  The  spleen  enlarged,  and  emboli 
occurred,  finally  cerebral  haemorrhage.  Approximate  dura- 
tion :  16  weeks.  Bacteriology  :  No  record.  Result  :  Death. 
Malignant  aortic  and  mitral  endocarditis. 

Case  18.  F.,  aged  8.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  ;  111  for  3  weeks  with  acute 
heart  disease.  Approximate  duration  :  3  weeks.  Bacteriology  : 
Strepto-diplococcus  from  aortic  valve.  Result :  Death.  Recent 
small  vegetations  on  mitral  and  tricuspid,  larger  on  aortic. 

Case  19.  F.,  aged  17.  Chorea  and  morbus  cordis  at  12 
years;  acute  rheumatism  at  15  years.  Main  symptoms  of 
final  illness  :  An  acute  illness  with  typhoidal  character  of  fever, 
commencing  with  a  stiff  neck.  Delirium,  purpura,  and  infarc- 
tions followed  mitral  and  aortic  disease.  Approximate  dura- 
tion :  .4  weeks.  Bacteriology  :  Strepto-diplococci  from  blood 
stream.  Result  :  Death.  Extensive  mitral  endocarditis 
spreading  on  the  anterior  flap  of  mitral  and  the  neighbouring 
aortic  cusp.     Infarctions  in  spleen  and  kidneys. 

Case  20.  F.,  aged  24.  Chorea  at  8,  13,  and  15  years. 
Main  symptoms  of  final  illness  :  Six  months  previously  acute 
rheumatic  arthritis,  since  then  never  well,  severe  aortic  and 
mitral  disease — persistent  irregular  fever,  infarctions  in  spleen 
and  kidneys.  Approximate  duration  :  8  weeks.  Bacterio- 
logy :  Strepto-diplococcus  from  blood.  Result  :  Death.  No 
post-mortem. 

Case  21.  F.,  aged  48.  Acute  rheumatism  at  38  years. 
Main  symptoms  of  final  illness  :  Failing  health  for  12  months — 
signs  of  cardiac  asystole  with  irregular  fever  and  aortic  and 


340  MITRAL  AND  AORTIC  DISEASE 

mitral  disease.  Approximate  duration  :  Gradual.  Bacterio- 
logy :  No  record.  Result  :  Death.  Malignant  endocarditis, 
aortic  and  mitral. 

Case  22.  M.,  aged  28.  Acute  rheumatism  at  18  years  and 
minor  attacks  since.  Main  symptoms  of  final  illness  :  Acute 
illness — typhoidal  in  character,  high  fever,  aortic  and  mitral 
disease  with  multiple  embolism.  Approximate  duration  : 
6  days'  acute  illness.  Bacteriology  :  (  No  record.  Result  : 
Death.     Malignant  aortic  and  mitral  disease. 

Case  23.  F.,  aged  27.  Acute  rheumatism  at  13  and  17 
years.  Main  symptoms  of  final  illness  :  Failing  health  for 
8  months  with  moderate  irregular  fever.  Aortic  and  mitral 
disease  and  renal  and  splenic  infarctions.  Approximate 
duration  :  5  weeks'  acute  illness.  Bacteriology  :  Negative. 
Result  :   Death.     No  post-mortem. 

Case  24.  F.,  aged  12.  Acute  rheumatism  at  7  years. 
Main  symptoms  of  final  illness  :  Mitral  disease,  later  developed 
aortic  regurgitation  with  high  irregular  fever  and  hematuria. 
Approximate  duration  :  10  weeks.  Bacteriology  :  Negative. 
Result  :    Left  with  the  diagnosis  of  malignant  endocarditis. 

Case  25.  F.,  aged  32.  Acute  rheumatism  and  chorea  as  a 
child.  Main  symptoms  of  final  illness  :  5  months'  history  of 
pains  in  the  joints  and  limbs,  6  months  under  observation  with 
irregular  fever,  aortic  and  mitral  disease,  pallor  and  emaciation. 
Approximate  duration  :  n  months.  Bacteriology  :  Negative. 
Result  :   Left  with  active  fever  thought  to  be  malignant. 

Group  II 

Transitional  Cases 

When  experimental  endocarditis  is  produced  with  the 
diplococcus,  whether  isolated  from  a  simple  or  malignant 
rheumatic  endocarditis,  every  grade  of  severity  may  result. 
Recovery  may  occur  or  speedy  death,  and  vegetations  of  all 
sizes  may  develop.  It  is  impossible  when  dealing  with  this 
experimental  endocarditis  to  justify  the  use  of  the  terms 
"  simple  "  and  "  malignant,"  and  it  is  evident  enough  that  the 
particular  result  is  a  question  of  the  virulence  of  the  cardiac 
infection.  If  this  is  the  case  with  a  small  animal  such  as  a 
rabbit  whose  cardiac  valves  are  so  minute  and  whose  resistance 
is  so  comparatively  weak,  it  is  much  more  evident  in  man,  in 


OF  RHEUMATIC  ORIGIN  341 

whom  the  resistance  to  the  rheumatic  infection  is  so  consider- 
able and  in  whom  the  infection  we  can  hardly  believe  occurs  in 
such  a  gross  fashion  as  by  the  method  of  intravenous  inocula- 
tion. One  link,  however,  in  the  chain  is  necessarily  wanting 
in  human  pathology.  We  are  not  able,  when  we  wish  to 
observe  the  particular  phase  of  an  endocarditis,  to  look  and 
see. 

Transitional  cases  of  rheumatic  endocarditis,  by  which  then 
we  imply  cases  hovering  on  the  border  line  of  the  divisions, 
simple  or  non-infective,  and  malignant  or  infective  endocarditis, 
are  of  frequent  occurrence. 

In  records  we  repeatedly  meet  with  cases  which  are  thought 
to  be  malignant  and  have  quieted  down,  or  have  been  con- 
sidered simple  and  proved  to  be  malignant.  From  time  to 
time  a  post-mortem  examination  shows  us  evidence  of  an  old 
malignant  process  in  a  valve  by  the  presence  of  a  large  calcified 
vegetation.  There  is,  however,  no  necessity  for  this  particular 
evidence,  for  the  malignancy  does  not  depend  Upon  the  size 
and  shape  of  vegetations  but  rather  upon  the  virulence  and 
number  of  the  infective  agent. 

As  an  example  in  illustration  may  be  quoted  the  following 
case  :  A  girl  of  twelve  had  suffered  from  an  attack  of  acute 
rheumatism  three  months  before  she  came  under  observation. 
From  this  attack  she  never  thoroughly  recovered  and  a  relapse 
of  polyarthritis  occurred,  with  a  slowly  progressive  endo- 
carditis of  the  mitral  and  aortic  valves.  When  death  occurred, 
five  months  later  from  cerebral  embolism,  a  calcareous  mass 
of  vegetation  was  found  upon  the  cusp  of  the  aortic  valve, 
and  on  the  thickened  mitral  valve  there  were  small  recent 
vegetations. 

This  group  of  transitional  cases  is  purely  artificial  and  is  not 
likely  to  content  anyone,  for  it  is  built  up  partly  upon  clinical, 
partly  upon  experimental,  and  partly  upon  pathological 
evidence,  and  in  some  cases  reliance  has  to  be  placed  upon  one 
source,  in  others  upon  another  source  of  evidence. 

We  have,  we  repeat,  only  used  the  term  here  in  order  to 
show  how  advisable  it  is  to  abandon  the  terms  "  simple  "  and 
"malignant"  as  applied  to  rheumatic  endocarditis,  and  by 
the  formation  of  such  a  group  to  do  what  little  we  can  to 
break  down  the  barrier  caused  by  the  terms  "  infective  "  and 
"  non-infective  "  endocarditis. 


342  MITRAL  AND  AORTIC  DISEASE 

The  examples  that  we  give  in  this  group  can  be  supplemented 
by  others  in  Group  I  and  Group  III. 

Group  No.  II 

Transitional  Cases.     Linked  to  Group  I  by  Cases  3,  6,  12, 
and  18  in  that  Group 

Case  i.  F.,  aged  10.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Admitted  for  multiple  arthritis 
and  heart  disease.  Ran  a  course  with  moderate  irregular 
fever.  The  spleen  enlarged  and  the  mitral  and  aortic  lesions 
proved  fatal.  Approximate  duration  :  n  weeks.  Bacterio- 
logy :  No  record.  Result :  Death.  The  vegetations  on  the 
mitral  and  aortic  valves  were  quite  small,  but  the  condition  of 
the  spleen  and  course  of  the  case  were  in  accordance  with 
malignant  endocarditis.     There  was  no  pericarditis. 

Case  2.  F.,  aged  12.  Acute  rheumatism :  An  attack 
3  months  before,  never  well  since.  Main  symptoms  of  final 
illness  :  For  many  weeks  slowly  losing  ground  with  multiple 
arthritis.  Aortic  and  mitral  disease.  Fever  for  the  last 
3  weeks  continuous,  and  finally  cerebral  embolism.  Approxi- 
mate duration  :  20  weeks.  Bacteriology  :  Negative.  Result  : 
Death.  The  mitral  valve  was  thickened  and  there  were  some 
recent  small  vegetations.  The  aortic  showed  a  calcareous 
mass  on  one  of  the  segments — suggesting  a  healed  malignant 
vegetation. 

Case  3.  M.,  aged  46.  Chorea  at  9  years.  Main  symptoms 
of  final  illness  :  A  long  illness  commencing  with  polyarthritis. 
Mitral  disease  was  followed  by  the  appearance  of  aortic  disease. 
There  was  continued  fever,  with  enlargement  and  tenderness 
of  the  spleen,  and  blood  and  albumin  in  the  urine.  Approxi- 
mate auration  :  16  weeks.  Bacteriology  :  Negative.  Result  : 
There  was  recovery  from  all  the  acute  symptoms.  It  is  difficult 
to  explain  the  clinical  course  except  as  due  to  a  transient 
malignancy. 

Case  4.  F.,  aged  44.  Rheumatic  fever  at  25  and  34  years. 
Main  symptoms  of  final  illness  :  Admitted  with  aortic  and 
mitral  disease  with  continuous  irregular  fever ;  developed 
haemoptysis  and  sudden  pain  in  the  left  side.  Approximate 
duration  :  9  weeks.  Bacteriology  :  Negative.  Result  :  There 
was  a  slow  recovery.     All  the  acute  symptoms  subsided. 


OF  RHEUMATIC  ORIGIN  343 

Case  5.  M.,  aged  13.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Developed  aortic  and  mitral 
disease  with  irregular  fever.  The  clinical  diagnosis  was 
malignant  endocarditis.  Approximate  duration  :  10  weeks. 
Bacteriology  :  Negative.  Result :  Relieved.  All  acute  symptoms 
disappeared. 

Case  6.  M.,  aged  38.  Acute  rheumatism  :  3  attacks. 
Main  symptoms  of  final  illness  :  Aortic  and  mitral  disease  with 
persistent  fever  for  7  weeks  and  cerebral  embolism.  Later 
signs  of  asystole.  Approximate  duration  :  12  weeks.  Bac- 
teriology :  Negative.  Result  :  Relieved.  Eventually  all  acute 
symptoms  subsided  and  the  patient  made  a  partial  recovery. 

Case  7.  M.,  aged  28.  Acute  rheumatism  at  24  years. 
Main  symptoms  of  final  illness  :  Admitted  for  active  mitral 
disease  ;  developed  aortic  regurgitation  with  persistent 
fever  for  12  weeks.  No  emboli  noted.  Approximate  dura- 
tion :  16  weeks.  Bacteriology  :  Negative.  Result  :  Relieved. 
Thought  to  be  malignant,  but  the  acute  symptoms  quieted 
down. 

Case  8.  M.,  aged  58.  Acute  rheumatism  at  30  and  42 
years.  Main  symptoms  of  final  illness  :  A  case  of  aortic  and 
mitral  disease  with  irregular  fever  for  3  months  and  blood  and 
albumin  in  the  urine.  Approximate  duration  :  12  weeks. 
Bacteriology  :    No  record.     Result  :   Relieve  7. 

Case  9.  F.,  aged  22.  Acute  rheumatism  as  a  child ; 
repeated  attacks  since.  Main  symptoms  of  final  illness  : 
Admitted  with  aortic  and  mitral  disease,  irregular  fever, 
hasmaturia,  and  ophthalmoplegia.  Recovered  partially,  but 
5  months  later  readmitted  with  nephritis.  Approximate  dura- 
tion :  4  weeks.  Bacteriology  :  No  record.  Result  :  Death. 
The  necropsy  showed  old  pericarditis.  Thickened  mitral  and 
aortic  valves,  a  large  spleen.  Large  white  kidneys,  with  scars 
of  previous  infarctions. 

Case  10.  F.,  aged  25.  Acute  rheumatism  at  17  years. 
Main  symptoms  of  final  illness  :  Admitted  with  slight  fever  ; 
ophthalmoplegia,  renal  infarctions.  Approximate  duration  : 
7  weeks.     Bacteriology;:    Negative.     Result  :   Relieved. 

Case  ii.  M.,  aged  15-17.  Acute  rheumatism  at  12  and 
13  years.  Main  symptoms  of  first  illness  (at  15)  \:  Arthritis 
and  mitral  and  aortic  disease,  fever.  Approximate  duration  : 
4  weeks.     Bacteriology  :   None  made.     Result  :    Simple  acute 


344  MITRAL  AND  AORTIC  DISEASE 

rheumatism.  Main  symptoms  of  second  illness  (at  16)  : 
Carditis  and  high  irregular  fever  for  8  weeks.  Approximate 
duration  :  12  weeks.  Bacteriology :  No  record.  Result  : 
Suspected  to  be  malignant.  Main  symptoms  of  third  illness 
(at  17)  :  Carditis  with  100  da3rs'  fever,  pleurisy.  Approximate 
duration  :  17  weeks.  Bacteriology  :  Negative.  Result  : 
Suspected  to  be  malignant  but  recovered. 

Case  12  F.,  aged  14.  Acute  rheumatism  at  11  years. 
Main  symptoms  of  final  illness  :  Admitted  with  polyarthritis, 
aortic  and  mitral  disease.  There  were  no  evidences  of 
embolism,  but  persistent  fever  for  9  weeks.  Approximate 
duration  :  9  weeks.  Bacteriology  :  No  record.  Result  : 
Relieved. 

Case  13.  F.,  aged  10.  Chorea  and  rheumatism  at  8  and 
9  years.  Main  symptoms  of  final  illness  :  Admitted  with 
polyarthritis,  aortic  and  mitral  disease,  persistent  fever  for 
9  weeks.  Approximate  duration  :  9  weeks.  Bacteriology  : 
No  record.  Result  :  Death.  Adherent  pericardium.  Aortic 
and  mitral  endocarditis  of  the  acute  rheumatic  type,  but  the 
spleen  enlarged. 

Group  III 

Acute  Rheumatic  Heart  Disease  {Simple  Tvpe) 

This  group  needs  no  explanation.  The  classical  examples 
are  found  in  the  young,  and  the  fatal  first  attacks  are  valuable 
illustrations  of  the  fact  that  death  results  from  a  pancarditis, 
and  not  from  the  simple  endocarditis.  Here  we  would  again 
repeat  that  in  most  of  the  opportunities  for  examining  the 
vegetations  of  simple  rheumatic  endocarditis  the  actual  process 
in  the  valves  is  in  a  stage  of  retrogression  ;  it  is  only  in  rare 
exceptions  that  a  condition  can  be  obtained  comparable  to  an 
early  experimental  endocarditis  in  which  an  animal  can  be 
killed  as  soon  as  the  signs  develop. 

In  several  instances  the  cases  with  recurrent  attacks  of 
rheumatism  illustrate^the  increasing'obstinacy  of  the  cardiac 
infection,  with  its  repetition,  and  also  show  that  the  relation  of 
a  recurrent  attack  to  previous  ones  precisely  resembles  that 
which  exists  between  the  malignant  cases  and  a  previous  attack 
of 'acute  rheumatism,  for  the  time  interval  may  be  short  or 
long. 


OF  RHEUMATIC  ORIGIN  345 


Group  No.  Ill 

Acute  Rheumatic  Endocarditis.     Linked  up  to  Group  II 
by  Cases  11,  12,  and  13  in  that  Group  and  3,   9,   and 

10  in  this 

Case  i.  M.,  aged  4^.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Polyarthritis,  subsiding. 
Aortic  and  mitral  disease,  pericarditis  and  nodules,  persistent 
fever.  Approximate  duration  :  12  weeks.  Bacteriology  : 
No  record.  Result  :  Death.  Subacute  pericarditis,  acute 
simple  aortic  and  mitral  endocarditis. 

Case  2.  M.,  aged  9.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  5  weeks'  fever  with  arthritis, 
nodules,  and  aortic  and  mitral  disease.  Approximate  dura- 
tion :  five  "weeks.  Bacteriology:  No  record.  Result:  Death. 
Acute  simple  aortic  and  mitral  endocarditis. 

Case  3.  F.,  aged  9^.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Arthritis,  carditis  and  chorea; 
persistent  irregular  fever.  Approximate  duration  :  five  weeks. 
Bacteriology  :  Strepto-diplococcus  isolated.  Result  :  Death. 
Acute  simple  endocarditis,  though  aortic  vegetations  larger, 
resembling  those  of  a  malignant  case.     Recent  pericarditis. 

Case  4.  M.,  aged  9.  Acute  rheumatism  at  8  years  (six 
months  ill).  Main  symptoms  of  final  illness  :  Acute  endo- 
carditis and  nodules  ;  nine  weeks'  fever.  Approximate  dura- 
tion :  ten  weeks.  Bacteriology  :  No  record.  Result  :  Death. 
Adherent  pericardium.  Mitral  and  aortic  endocarditis,  recent 
vegetations,  thickened  valves. 

Case  5.  M.,  aged  10-11^.  Acute  rheumatism  :  First 
attack  at  10  years  ;  second  attack  at  n|-  years.  Main 
symptoms  of  first  illness  :  Arthritis,  persistent  fever  for  many 
weeks,  of  the  typhoidal  type  ;  aortic  and  mitral  disease. 
Approximate  duration  :  twenty  weeks.  Bacteriology  :  None 
made.  Main  symptoms  of  second  illness  :  Asystole.  Approxi- 
mate duration  :  two  weeks.  Bacteriology  :  No  record. 
Result  :  Death.  Thickened  aortic  valves,  with  minute 
vegetations,  aortic  atheroma. 

Case  6.  F.,  aged  7.  Acute  rheumatism  at  6  years.  Main 
symptoms   of  final  illness  :    Arthritis.     Continuous  irregular 


346  MITRAL  AND  AORTIC  DISEASE 

fever,  aortic  and  mitral  disease.  Approximate  duration  : 
twelve  weeks.  Bacteriology  :  No  record.  Result  :  Death. 
Slight  recent  aortic  endocarditis.     Old  and  recent  mitral. 

Case  7.  F.,  aged  6\.  Acute  rheumatism  at  4  and  5  years 
with  pericarditis.  Main  symptoms  of  final  illness  :  Asystole, 
with  slight  fever.  Approximate  duration  :  five  weeks.  Bac- 
teriology :  No  record.  Result  :  Death.  Mitral  aortic  and 
tricuspid  endocarditis  of  the  acute  rheumatic  type.  No  evidence 
of  pericarditis. 

Case  8.  F.,  aged  16.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Commenced  with  polyarthritis, 
ten  weeks'  fever,  gradually  subsiding.  Aortic  and  mitral  dis- 
ease. Approximate  duration  :  thirteen  weeks.  Bacteriology  : 
No  record.     Result  :   Relieved. 

Case  9.  F.,  aged  6-8.  Acute  rheumatism  :  First  attack 
at  6  years  ;  second  attack  at  7  years  ;  third  attack  at  8  years. 
Main  symptoms  of  first  illness  :  Arthritis,  chorea,  nodules, 
persistent  carditis,  aortic  and  mitral  disease,  waves  of  fever 
extending  over  many  weeks.  Approximate  duration :  At 
least  eighteen  weeks.  Bacteriology  :  No  record.  Result  :  Re- 
lieved. Main  symptoms  of  second  illness  :  Carditis,  persistent 
fever.  Approximate  duration  :  Twelve  weeks.  Bacteriology  : 
None  made.  Result  :  Relieved.  Main  symptoms  of  third 
illness  :  Ten  days'  fever,  asystole.  Approximate  duration  : 
Ten  days.  Bacteriology :  Strepto-diplococcus  isolated  from 
mitral  valve.  Result  :  Death.  Recent  and  old  pericarditis, 
aortic  valves  inflamed  from  base  to  margin. 

Case  10.  M.,  aged  ii-i6£.  Chorea  at  3  years,  acute 
rheumatism  at  n,  12,  14,  16,  and  i6£  years.  Main  symptoms 
of  first  illness  :  Aortic  and  mitral  disease,  nodules,  persistent 
fever.  Approximate  duration  :  Twenty  weeks.  Bacteriology  : 
No  record.  Result  :  Simple  mitral  endocarditis.  Main 
symptoms  of  second  illness  :  Sent  in  for  "  a  rest,"  persistent 
fever  and  tachycardia  for  three  weeks.  Approximate  dura- 
tion :  three  weeks.  Bacteriology  :*  No  record.  Result  : 
Relieved.  Main  symptoms  of  third  illness  :  Three  weeks' 
palpitation  and  fever.  Approximate  duration  :  Five  weeks. 
Bacteriology  :  No  record.  Result  :  Relieved.  Main  symp- 
toms of  fourth  illness  :  Ten  weeks'  pericarditis  and  carditis. 
Approximate  duration  :  Twelve  weeks.  Bacteriology  :  Blood 
culture  negative.     Result  :    Relieved.     Fifth  illness.     Result  : 


OF  RHEUMATIC  ORIGIN  347 

Sudden  death.  No  post-mortem  ;  probably  the  simple  type. 
Note  persistent  carditis  with  fever. 

Case  ii.  F.,  aged  17.  Acute  rheumatism  at  10  years  and 
two  attacks  since.  Main  symptoms  of  final  illness  :  Admitted 
with  mitral  regurgitations  and  slight  fever  ;  developed  aortic 
regurgitations  and  died  suddenly.  Approximate  duration  : 
Three  weeks.  Bacteriology :  No  record.  Result  :  Death. 
No  post-mortem. 

Case  12.  M.,  aged  22.  Acute  rheumatism  at  11  and  17 
years.  Main  symptoms  of  final  illness  :  Multiple  arthritis. 
Aortic  and  mitral  disease  with  irregular  outbursts  of  fever, 
synchronous  with  which  there  was  precordial  pain.  Approxi- 
mate duration  :  Eight  weeks.  Bacteriology  :  No  record. 
Result  :   Relieved. 

Case  13.  M.,  aged  22.  Acute  rheumatism  at  18  and  20 
years.  Main  symptoms  of  final  illness  :  Five  months'  history 
of  recurrent  anginal  attacks,  also  multiple  arthritis,  aortic  and 
mitral  disease  and  recurrent  attacks  of  fever.  Approximate 
duration  :  Eight  weeks.  Bacteriology  :  No  record.  Result  : 
Relieved. 

Case  14.  M.;  aged  50.  Acute  rheumatism  in  childhood 
and  at  25  years.  Main  symptoms  of  final  illness  :  Aortic  and 
mitral  disease,  with  irregular  fever  for  seven  days.  Approxi- 
mate duration  :  Six  weeks.  Bacteriology :  No  record. 
Result  :   Relieved. 

Case  15.  F.,  aged  10.  Acute  rheumatism  at  7  and  8 
years.  Main  symptoms  of  final  illness  :  Polyarthritis,  aortic 
and  mitral,  tachycardia,  high  irregular  fever  followed  by  a 
normal  temperature  and  relapse.  Approximate  duration  : 
Five  weeks.  Bacteriology :  No  record.  Result  :  Relieved. 
Severe  type  of'simple^carditis. 

Case  16.  M.,  aged  38.  History  of  acute  rheumatism  at  6; 
12,  and  21  years.  Main  symptoms  of  final  illness  :  Mitral  and 
aortic  disease  with  three  attacks  of  fever,  in  one  of  which  an 
attack  of  pericarditis.  Approximate  duration  :  Ten  weeks. 
Bacteriology  :   No  record.     Result  :   Relieved. 

Case  17.  F.,  aged  20.  Acute  rheumatism  at  6  and  12 
years  ;  chorea  at  15  years.  Main  symptoms  of  final  illness  : 
Double  mitral  and  aortic  regurgitation  with  slight  transient 
fever.  Approximate  duration  :  Four  weeks.  Bacteriology  : 
No  record.     Result  :   Relieved. 


348  MITRAL  AND  AORTIC  DISEASE 

Case  18.  M.,  aged  25.  Acute  rheumatism  :  Several  mild 
attacks.  Main  symptoms  of  final  illness  :  Polyarthritis, 
transient  fever,  mitral  and  aortic  disease.  Approximate 
duration  :  Seven  weeks.  Bacteriology  :  No  record.  Result  : 
Relieved. 

Case  19.  M.,  aged  32.  Acute  rheumatism  at  11,  16,  and 
26  years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease,  left  with  a  rising  temperature.  Approximate  dura- 
tion :  Thirteen  weeks.  Bacteriology  :  No  record.  Result  : 
Left  at  own  request,  nature  of  endocarditis  doubtful. 

Case  20.  F.,  aged  18.  Acute  rheumatism  :  Six  attacks. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease,  three 
weeks'  irregular  fever,  pericarditis,  several  relapses  of  fever. 
Approximate  duration  :  Thirteen  weeks.  Bacteriology  :  No 
record.     Result  :   Relieved.     Severe  type. 

Case  21.  F.,  aged  24.  Chorea  at  9  years  ;  acute  rheu- 
matism at  16  years.  Main  symptoms  of  final  illness  :  Mitral 
and  aortic  disease  with  slight  fever.  Approximate  duration  : 
Five  weeks.     Bacteriology  :    No  record.     Result  :   Relieved.  , 

Case  22.  F.,  aged  20.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Multiple  arthritis,  aortic  and 
mitral  regurgitations,  always  a  slightly  swinging  temperature. 
Approximate  duration  :  Eleven  weeks.  Bacteriology  :  Blood 
culture  negative.  Result  :  Relieved.  Note  persistent  slight 
fever. 

Case  23.  M.,  aged  13.  Acute  rheumatism  at  ii\  years. 
Main  symptoms  of  final  illness  :  Aortic  and  mitral  disease, 
arthritis,  nodules,  slight  fever.  Approximate  duration  :  Seven 
weeks.     Bacteriology  :   No  record.     Result  :   Relieved. 

Case  24.  M.,  aged  27.  Acute  rheumatism  at  21  years. 
Main  symptoms  of  final  illness  :  Dyspnoea,  mitral  and  aortic 
disease,  slight  irregular  fever.  Approximate  duration  :  Five 
weeks.     Bacteriology  :  I  No  record.     Result:   Relieved. 

Case  25.  M.,  aged  21.  Acute  rheumatism  at  10  and  n 
years.  Main  symptoms  of  final  illness  :  Subacute  arthritis, 
mitral  and  aortic  disease,  slight  fever.  Approximate  duration  : 
Three  weeks.     Bacteriology:   No  record.     Result:    Relieved. 

Case  26.  M.,  aged  24.  Acute  rheumatism  at  11  years. 
Main  symptoms  of  final  illness  :  Arthritis,  mitral  and  aortic 
disease,  and  irregular  fever.  Approximate  duration  :  Seven 
weeks.     Bacteriology  :   No  record.     Result  :   Relieved. 


OF  RHEUMATIC  ORIGIN  349 

Case  27.  M.,  aged  22.  Acute  rheumatism  :  First  attack. 
Main  symptoms  of  final  illness  :  Arthritis  followed,  by  mitral 
and  then  aortic  regurgitations,  always  a  slight  fever,  never 
rising  above  100  °  F.  Approximate  duration  :  Seventeen 
weeks.  Bacteriology  :  No  record.  Result  :  Relieved.  Note 
the  mild  but  progressive  course. 

Case  28.  F.,  aged  35.  Acute  rheumatism  at  14  years. 
Main  symptoms  of  final  illness  :  Arthritis,  mitral  and  aortic 
disease  and  slight  fever.  Approximate  duration  :  Five  weeks. 
Bacteriology  :   No  record.     Result  :  Relieved. 

Case  29.  F.,  aged  11.  Acute  rheumatism  at  8  and  9  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease  ;  only 
in  hospital  ten  days.  Approximate  duration  :  Ten  days. 
Bacteriology  :   No  record.     Result  :   Relieved. 

Case  30.  F.,  aged  34,  Acute  rheumatism  :  Six  attacks. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease. 
Approximate  duration  :  Five  weeks.  Bacteriology  :  No 
record.     Result  :   Relieved. 

Case  31.  M.,  aged  10.  Acute  rheumatism  at  6  years. 
Main  symptoms  of  final  illness  :  Pericarditis,  aortic  and  mitral 
disease,  nodules  and  arthritis,  fever  for  fourteen  days,  ill 
twelve  weeks.  Approximate  duration  :  Twelve  weeks.  Bac- 
teriology :  No  record.  Result  :  Death.  Thickened  aortic 
and  mitral  with  recent  vegetations  (small).  Recent  peri- 
carditis. 

Case  32.  F.,  aged  19.  Rheumatism  and  chorea  at  13 
years.  Main  symptoms  of  final  illness  :  Severe  aortic  and 
mitral  disease  with  continuous  fever  for  five  weeks  ;  anginal 
attacks.  Approximate  duration  :  Five  weeks.  Bacteriology  : 
No  record.  Result  :  Relieved.  Note  prolonged  fever,  car- 
ditis, and  angina. 

Case  33.  F.,  aged  38.  Acute  rheumatism  at  14  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease, 
admitted  with  transient  polyarthritis  and  fever.  Approximate 
duration  :  Five  weeks.  Bacteriology  :  No  record.  Result  : 
Relieved. 

Cases  in  Group  IV 

The  last  group  of  cases  will  not  need  any  prolonged  explana- 
tion, for  they  are  examples  of  heart  scars  with  consequent 
mechanical  disabilities.     There  is  a  sufficient  number  of  fatal 


350  MITRAL  AND  AORTIC  DISEASE 

cases  among  them  in  which  a  necropsy  has  proved  the  reality 
of  such  an  interpretation,  and  their  chief  importance  is  to 
emphasise  the  power  that  the  human  frame  possesses  to  resist 
the  rheumatic  infection.  This  very  fact  bringing  it  strictly 
into  hne  with  other  great  infections  only  serves  to  throw  into 
relief  the  overwhelming  probability  that  these  healing  pro- 
cesses may  also  fail,  as  they  do  undoubtedly  succeed,  in  such  a 
struggle.  What  an  assumption  it  must  be  to  assert  that  such 
an  infection  as  the  rheumatic  could  always  be  overcome  in  the 
cardiac  valves  !  Even  if  we  were  deprived  of  all  the  clinical, 
pathological,  and  experimental  evidence  we  now  possess  such 
an  assumption  would  be  open  to  the  gravest  questioning,  but 
with  such  evidence  at  hand  it  must  surely  be  abandoned  as  a 
survival  of  an  older  pathology  which  existed  when  acute 
rheumatism  was  looked  upon  as  of  nervous  or  lactic  acid 
origin.  Old  beliefs  die  very  hard,  and  oftentimes  in  medical 
literature  may  be  seen  the  strange  results  of  attempting  to 
graft  upon  an  old  stem  the  new  shoots  of  another  plant  of 
knowledge.  The  relationship  of  rheumatism  to  malignant 
endocarditis  is  a  beautiful  example  of  such  an  attempt.  Every 
sort  of  ingenious  device  has  been  invented  to  graft  the  old  stem 
with  the  new  shoots,  but  they  have  all  failed. 

Among  the  most  remarkable  must  be  placed  that  one  which 
suggests  that  rheumatism  is  a  mysterious  and  unknown 
disease  akin  to  simple  scarlet  fever,  upon  which  all  the  mani- 
festations are  to  be  grafted  as  secondary  infections.  When 
we  can  imagine  on  the  one  hand  a  scarlet  fever  which  is  not 
infectious  and  is  without  a  rash  save  in  exceptional  cases,  and 
on  the  other  a  rheumatism  which  is  infectious  and  which 
possesses  no  manifestations  except  possibly  a  sore  throat  and 
an  occasional  rash,  we  may  be  able  to  appreciate  the  likeness 
between  these  two  diseases.  For  us  an  infectious  disease  such 
as  scarlet  fever,  whether  complicated  by  secondary  infections 
or  not,  possesses  a  peculiarity  of  its  own,  viz.  its  infectivity. 
Whereas  acute  rheumatism,  deprived  of  its  manifestations, 
is  a  disease  still  to  be  discovered,  as  also  would  be  in  our 
opinion  a  tuberculosis  or  pneumococcal  infection  without  its 
manifestations. 


OF  RHEUMATIC  ORIGIN  351 

Group  No.  IV 

Chronic  Heart  Disease  due  to  previous  Rheumatic  Endocarditis 

A .  Cases  showing  chiefly  aortic  symptoms 

Case  i.  M.,  aged  63.  Acute  rheumatism  :  Three  attacks  ; 
heart  disease  at  13  years.  Main  symptoms  of  final  illness  : 
Two  days'  illness.  Sudden  death,  aortic  type,  mitral  and 
aortic  disease.  Approximate  duration  :  Two  days.  Result  : 
Death.     Calcified  valves. 

Case  2.  M.,  aged  42.  Much  rheumatism.  Main  symp- 
toms of  final  illness  :  Angina  pectoris — dyspnoea,  aortic  and 
mitral  disease.  Approximate  duration  :  Many  weeks.  Result  : 
Death.     Thickened  valves  and  aortic  atheroma. 

Case  3.  M.,  aged  40.  Acute  rheumatism  at  27.  Main 
symptoms  of  final  illness  :  Mitral  and  aortic  disease,  angina 
pectoris.  Approximate  duration  :  Four  weeks.  Result  : 
Relieved. 

Case  4.  M.,  aged  40.  Acute  rheumatism :  Repeated 
attacks.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease  with  angina.  Approximate  duration  :  Six  weeks. 
Result  :   Relieved. 

Case  5.  F.,  aged  14.  Acute  rheumatism  :  Slight.  Main 
symptoms  of  final  illness  :  Mitral  and  aortic  disease,  pallor, 
pain  in  chest.  Approximate  duration  :  Nine  days.  Result  : 
Relieved. 

Case  6.  M.,  aged  28.  Acute  rheumatism  at  18  years  and 
since.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease,  dyspnoea.  Approximate  duration  :  Seven  days. 
Result  :   Left  at  his  own  request. 

Case  7.  M.,  aged  48.  Acute  rheumatism  at  35  and  39 
years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease,  angina.  Approximate  duration  :  Three  weeks.  Result  : 
Relieved. 

B.  Cases  showing  chiefly  mitral  symptoms 

Case  i.  M.,  aged  38.  Acute  rheumatism  :  Several  attacks. 
Main  symptoms  of  final  illness  :  Alcoholism.  Mitral  and 
aortic  disease,  jaundice,  dropsy,  dyspnoea.  Approximate 
duration  :  Eleven  weeks.  Result  :  Death.  Sclerosis  of  aortic 
and  mitral  valves. 


352  MITRAL  AND  AORTIC  DISEASE 

Case  2.  M.,  aged  50.  Acute  rheumatism  at  8,  25,  36,  and 
49  years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic. 
(Edema,  dyspnoea,  &c.  ;  asystole.  Approximate  duration ; 
Many  weeks.  Result  :  Death.  Calcined  aortic  and  mitral 
valves  ;  shortening  of  chordae  tendinese. 

Case  3.  M.,  aged  72.  Acute  rheumatism  at  17  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic.  Myocardial 
weakness.  Asystole.  Approximate  duration :  Four  weeks. 
Result :  Death.   Thickened  mitral  and  aortic  valves.    Atheroma. 

Case  4.  F.,  aged  52.  Acute  rheumatism  at  40  years.  Main 
symptoms  of  final  illness  :  Mitral  and  aortic.  Asystole,  with 
oedema,  &c.  Approximate  duration  :  Four  weeks.  Result  : 
Relieved. 

Case  5.  F.,  aged  60.  Acute  rheumatism  :  Slight  attacks. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic.  Asystole, 
with  cyanosis  and  dropsy.  Approximate  duration  :  Five 
weeks.     Result  :  Relieved. 

Case  6.  F.,  aged  79.  Acute  rheumatism  :  Six  attacks. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic.  Asystole — 
mitral  type.  Approximate  duration  :  Five  weeks.  Result  : 
Relieved. 

Case  7.  M.,  aged  35.  Acute  rheumatism  at  20  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic.  Alcohol- 
ism, asystole.  Approximate  duration  :  Five  weeks.  Result  : 
Relieved. 

Case  8.  M.,  aged  20.  Acute  rheumatism  at  11  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic.  Asystole — 
mitral  type.  Approximate  duration  :  Three  weeks.  Result  : 
Relieved. 

Case  9.  F.,  aged  18.  Acute  rheumatism  at  13,  14  and 
15  years.  Main  symptoms  of  final  illness  :  Mitral  and 
aortic.  Approximate  duration  :  Two  weeks.  Result  : 
Relieved. 

Case  10.  F.,  aged  26.  Acute  rheumatism :  Repeated 
attacks.  Main  symptoms  of  final  illness  :  Mitral  and  aortic. 
Severe  asystole,  mitral  type.  Approximate  duration  :  Twenty- 
four  weeks.     Result  :  Relieved. 

Case  ii.  F.,  aged  20.  Acute  rheumatism  :  Six  attacks. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease. 
Signs  of  mitral  asystole.  Approximate  duration  :  Four  weeks. 
Result  :  Relieved. 


OF  RHEUMATIC  ORIGIN  353 

Case  12.  M.,  aged  40.  Acute  rheumatism  at  19  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease. 
Signs  of  mitral  asystole.  Approximate  duration  :  Ten  weeks. 
Result  :  Relieved. 

Case  13.  M.,  aged  48.  Acute  rheumatism  at  12  and  38 
years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease.  Signs  of  asystole.  Approximate  duration  :  Some 
weeks.     Result  :   Relieved. 

Case  14.  M.,  aged  22.  Acute  rheumatism  at  19  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease. 
Signs  of  asystole,  mitral.  Approximate  duration  :  Three 
weeks.     Result  :   Relieved. 

Case  15.  M.,  aged  22.  Acute  rheumatism  at  16  years. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease, 
prolonged  asystole.  Approximate  duration  :  Eighteen  months. 
Result  :   Relieved. 

Case  16.  F.,  aged  32.  Acute  rheumatism  at  14,  19,  21, 
23,  and  25  years.  Main  symptoms  of  final  illness  ;  Mitral  and 
aortic  disease,  with  palpitation.  Approximate  duration  : 
Seven  days.     Result  :   Relieved. 

Case  17.     F.,  aged  32.     Acute  rheumatism  at  17  and  31 
years.     Main  symptoms  of  final  illness  :    Mitral   and  aortic  . 
disease,  with  signs  of  mitral  asystole.     Approximate  duration  : 
Four  weeks.     Result  :   Relieved. 

Case  18.  F.,  aged  33.  Acute  rheumatism  as  a  child. 
Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease. 
Palpitation,  &c.  Approximate  duration  :  Ten  days.  Result  : 
Relieved. 

Case  19.  F.,  aged  21.  Acute  rheumatism  at  11  and  12 
years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease.  Anaemia,  palpitation,  &c.  Approximate  duration  : 
Many  months.     Result  :   Relieved. 

Case  20.  F.,  aged  28.  Acute  rheumatism  as  a  child  and 
at  18  years.  Main  symptoms  of  final  illness  :  Mitral  and  aortic 
disease.  Asystole.  Approximate  duration  :  Many  weeks. 
Result  :  Relieved. 

Case  21.     M.,   aged  14.     Acute  rheumatism  at   12  years. 

Main  symptoms  of  final  illness  :    Mitral  and  aortic  disease. 

Severe  asystole.    Approximate  duration  :  Four  weeks.    Result  : 

Death.     Aortic  and  mitral  valves  thickened,  adherent  pericardium. 

Case  22.     M.,   aged  30.     Acute  rheumatism  at   16  years. 

23 


354  MITRAL  AND  AORTIC  DISEASE 

Main  symptoms  of  final  illness  :  Mitral  and  aortic  disease. 
Signs  of  asystole.  Approximate  duration  :  Three  weeks  : 
Result  :   Relieved. 

We  wish  now  to  put  very  briefly  our  conception  of  acute 
rheumatism — or,  as  we  would  prefer  to  call  it,  rheumatism — 
side  by  side  with  the  pictures  of  other  similar  infections. 

i.  First  of  all  the  gonorrhceal  infection. 

From  a  local  focus  in  the  urethra  there  may  follow  a  systemic 
invasion  producing  multiple  arthritis  and  other  lesions,  includ- 
ing a  carditis.  The  arthritis  may  be  transient,  but  often  is 
exceedingly  stubborn  and  drifts  into  a  condition  of  rheumatoid 
arthritis.  The  heart  affection  may  be  a  pancarditis,  or  a 
transient  endocarditis,  or  a  malignant  endocarditis. 

2.  With  the  pneumococcal  infection  the  lungs  and  pleurae 
take  the  position  that  the  heart  occupies  in  rheumatism,  but 
arthritis  of  all  grades  of  severity  may  result,  and  also  a  carditis, 
in  which  suppurative  pericarditis  and  malignant  endocarditis 
are  liable  to  develop. 

3.  In  staphylococcal  infections,  from  a  local  infection  such 
as  an  acute  osteo-myelitis,  there  may  follow  multiple  arthritis 
and  multiple  nodular  subcutaneous  abscesses,  myocardial 
abscesses,  and  acute  malignant  endocarditis  may  all  result. 

4.  Virulent  streptococcal  infections  of  the  type  caused  by 
the  streptococcus  pyogenes  show  a  similar  picture.  The  arthritis, 
if  not  exceedingly  acute,  is  suppurative  ;  profound  myocardial 
poisoning  is  much  more  frequent  than  endocarditis,  and  this, 
when  it  occurs,  is  usually  malignant  in  type.  A  general 
septicaemia  is  frequent,  and  in  classical  cases  the  entire  process 
differs  widely  from  that  of  acute  rheumatism.  It  is  a  difference 
in  the  type  and  not  in  the  degree  of  virulence. 

5.  The  rheumatic  infection  from  such  a  focus  as  the  tonsil 
may  produce  an  arthritis  and  other  lesions,  including  a  carditis. 
Two  features  are  well  recognised.  One  is  that  the  arthritis  is 
usually  transient,  although  we  maintain  that  a  rheumatoid 
arthritis  may  result  from  this  infection.  The  other  is  the  great 
prominence  of  cardiac  lesions.  Carditis  is  very  frequent,  and 
both  simple  and  malignant  endocarditis  may  result. 

We  believe  that  this  conception  of  acute  rheumatism  as  a 
peculiar  streptococcal  infection  fills  a  gap  in  our  knowledge  of 
this  important  disease,  in  a  way  that  is  unequalled,  not  only 


OF  RHEUMATIC  ORIGIN  355 

for  its  simplicity,  but  for  the  completeness  of  the  explanation 
which  it  affords  of  the  symptoms  and  course  of  the  affection. 

The  strong  hereditary  element  in  the  disease  supports  the 
view  that  the  exciting  cause  possesses  some  peculiarity  by 
which  in  these  particular  tissues  it  can  form  the  special  poisons 
that  make  it  so  definite  an  affection. 

Concluding  Remarks 

We  believe  that  the  view  we  support  in  this  research  is  not 
one  of  academic  interest  or  a  mere  battle  of  words.  It  will  be 
a  distinct  gain  if  we  succeed  in  overthrowing  the  remarkable 
view  that  the  nature  of  rheumatic  endocarditis — whatever  the 
infection  may  be — is  always  benign  and  requires  an  added 
infection  to  produce  a  progressive  lesion.  The  survival  of 
such  a  view  implies  such  a  subversion  of  the  natural  principles 
of  the  infective  processes  as  to  unsteady  one's  whole  outlook 
upon  these  diseases.  The  disappearance  of  such  a  mystery,  on 
the  other  hand,  must  be  a  clear  gain  to  connected  thought 
upon  all  rheumatic  processes  and  a  forward  step  in  cardiac 
pathology. 

Far  more  important  is  its  bearing  upon  the  clinical  side  of 
malignant  endocarditis.  The  rheumatic  form  is  no  exception 
to  the  rule  that  it  is  a  disease  which  is  almost  invariably  fatal 
when  the  signs  are  well  established.  Theoretical  considerations 
lead  to  the  belief  that  occasional  recoveries  may  occur,  and 
there  is  good  clinical  evidence  in  support  ;  but  these  excep- 
tions are  rare,  and  our  series  alone  shows  the  great  fatality. 

We  are  doubtful  of  the  efficacy  of  serum  or  vaccine  at  present 
in  use,  though  we  would  neither  dispute  the  records  of  such 
recoveries  while  such  treatment  was  being  employed,  nor  the 
advisability  of  trying  any  method  that  holds  out  the  least 
prospect  of  success. 

It  is  the  prophylaxis  that  is  encouraged  by  our  investigations. 
There  must  clearly  be  some  peculiar  factors  at  work  to  produce 
the  progressive  endocarditis,  and  we  sometimes  find  suggestive 
evidence  in  support  of  this.  The  cardiac  rheumatism  may 
have  been  neglected,  the  patient  ill-fed,  the  surroundings 
unhealthy.  Anaemia — a  prominent  feature  of  some  rheumatic 
attacks — may  have  persisted,  and  this  in  our  opinion  favours 
the  malignant  process.  The  danger  of  large  unhealthy  tonsils 
in  the  rheumatic  is  well  established,  and  this  danger  can  be 


356  MITRAL  AND  AORTIC  DISEASE 

cautiously  dealt  with.  Above  all,  we  believe  that  more  clinical 
study  is  necessary  of  the  course  and  history  of  acute  rheumatic 
endocarditis.  We  believe  that  a  smouldering  activity  of  the 
rheumatic  process  is  more  common  than  is  suspected,  and 
very  possibly  we  may  not  yet  possess  the  necessary  clinical 
accuracy  for  ascertaining  the  limits  of  this  activity.  This 
seems  the  more  likely  when  we  bear  in  mind  that  even  a  gross 
and  progressive  lesion  may  elude  our  observation  until  the 
end  is  close  at  hand. 

There  is  more  hope  that  we  may  protect  a  patient  against 
the  development  of  a  known  danger  than  against  a  mysterious 
secondary  infection  which  prefers  scarred  valve  tissues  and 
which  appears  usually  without  any  particular  cause  or  reason. 

The  disappearance  of  the  terms  "malignant,"  "infective," 
or  "  pernicious  "  as  applied  to  endocarditis  will  be  a  great 
advantage,  and  the  substitution  of  the  term  "  active  "  will 
answer  every  purpose,  for  the  physician  can  judge  of  the 
degree  of  this  activity  by  the  well-known  signs  that  may 
arise.  "  Active  tuberculosis  "  expresses  sufficiently  a  progres- 
sive pulmonary  lesion,  and  we  need  no  term  "  malignant 
tuberculosis  ' '  to  bring  home  to  us  the  fact  that  the  activity  is 
getting  beyond  all  control.  Why  then  use  such  a  term  as 
"  malignant  endocarditis,"  or  perpetuate  such  an  unproven 
conception  as  a  non-infective  endocarditis,  by  the  use  of  the 
adjective  "  infective  "  ? 

REFERENCE 
Guy's  Hospital  Reports,  191 1,  p.  193. 


PART   II 

SUB-GROUP  F 

THE  CONCLUDING  PAPERS  OF  THE  SECOND  PART 
OF  THIS  VOLUME  DEAL  WITH  THE  VERY  INTER- 
ESTING PROBLEMS  OF  THE  METHODS  OF  ORIGIN 
OF  APPENDICITIS,  AND  THE  RELATION  OF  APPEN- 
DICITIS TO  RHEUMATISM.  THE  FIRST  PAPER 
WHICH  WAS  WRITTEN  ALMOST  EXACTLY  TEN 
YEARS  BEFORE  THE  SECOND,  HAS  BEEN  PLACED 
WITH  THE  OTHERS  IN  ORDER  TO  MAKE  THE 
INVESTIGATION  MORE  COMPLETE.  THE  LAST 
PAPER  HAS  NOT  BEEN  PUBLISHED  BEFORE, 
AND  IS  INCLUDED  AS  A  FURTHER  EXPRESSION 
OF  OUR  VIEWS  UPON  THE  EXPERIMENTAL, 
CLINICAL,  AND  PATHOLOGICAL  ASPECTS  OF  THE 
SUBJECT. 

XXIV.  ARTHRITIS  IN  ASSOCIATION  WITH  PERITYPHLITIS 

XXV.  A  FURTHER  CONTRIBUTION  TO  THE  STUDY  OF  RHEU- 
MATISM. THE  EXPERIMENTAL  PRODUCTION  OF 
APPENDICITIS  BY  THE  INTRAVENOUS  INOCULATION 
OF  THE  DIPLOCOCCUS  RHEUMATICUS. 

XXVI.  A  FURTHER  CONTRIBUTION  TO  THE  STUDY  OF  THE 
^ETIOLOGY  OF  APPENDICITIS  AS  A  BLOOD  INFEC- 
TION, WITH  PARTICULAR  REFERENCE  TO  THE 
TONSILS  AS  THE  PRIMARY  SEAT  OF  INFECTION 

XXVII.  OBSERVATIONS  UPON  APPENDICITIS  BASED  UPON 
A  COMPARATIVE  STUDY  OF  THE  MORBID  ANATOMY 
IN  THE  HUMAN  AND  EXPERIMENTAL  DISEASE 


357 


PAPER  NO.  XXIV 

ARTHRITIS  IN  ASSOCIATION  WITH 
PERITYPHLITIS 

(Reprinted  from  Transactions  of  the  Medical  Society  of  London, 

vol.  xxiv.) 

In  this  paper,  written  in  1900,  the  subject  of  appendicitis  and 
rheumatism  is  discussed  from  various  points  of  view.  The  opinions 
of  those  who  believe  that  there  is  a  direct  connection  between  the  two 
diseases  are  given,  and  some  clinical  evidence  added  in  support.  On 
the  other  hand,  the  possibility  of  other  explanations  of  the  apparent 
association  are  put  forward,  and  examples  are  given  of  pycemic  condi- 
tions following  appendicitis  and  simulating  rheumatism.  If  there  was 
a  direct  connection  between  rheumatism  and  appendicitis  it  appeared 
to  us  that  the  rheumatic  infection  of  the  appendix  was  a  lesion  which 
did  not  occur  in  acute  rheumatism  of  the  ordinary  type.  It  was, 
however,  conceivable  that  rheumatism  affecting  the  alimentary  canal 
might  spare  the  other  systems,  just  as  some  cases  of  rheumatic  arthritis 
appear  to  locate  themselves  in  the  joints  alone  or  in  the  joints  and 
muscles,  sparing  the  heart  and  nervous  system. 

The  association  of  arthritis  with  perityphlitis,  though  not  a 
common  occurrence,  has  attracted  some  attention,  because  it 
has  seemed  likely  to  throw  light  upon  the  aetiology  of  peri- 
typhlitis. Some  observers,  who  have  noticed  this  association, 
have  advanced  the  suggestion  that  rheumatic  fever  is  an 
important  cause  in  the  production  of  perityphlitis  and  have 
brought  forward  evidence  in  its  support.  This  evidence  for 
convenience  is  classified  under  four  headings.  Firstly,  there 
is  the  occurrence  of  perityphlitis  in  the  subjects  of  acute 
rheumatism  ;  secondly,  the  occurrence  of  a  polyarthritis, 
resembling  that  of  acute  rheumatism,  coincident  with,  or 
shortly  after,  an  attack  of  perityphlitis  ;  thirdly,  there  is  the 
reaction  of  some  cases  of  perityphlitis  to  treatment  with 
salicylates  ;  and  lastly,  there  is  the  structural  analogy  of  the 
tonsils  and  appendix  vermiformis. 

359 


36o  ARTHRITIS 

To  take  the  last  of  these  first,  Bland-Sutton,  Kelynack,  Mayo 
Robson,  and  others  have  proved  that  lymphoid  tissue  is 
present  in  the  appendix.  Those  who  support  the  rheumatic 
hypothesis  point  out  that  cold  is  a  factor  in  appendicitis  and 
also  in  rheumatism.  They  compare  the  tonsil  and  the 
appendix,  and,  guided  by  the  undoubted  fact  that  tonsillitis  is 
frequently  the  earliest  symptom  of  rheumatic  fever,  conclude 
that,  in  some  cases,  perityphlitis  may  also  be  an  early  symptom 
of  the  same  disease.  This  argument  is  both  interesting  and 
ingenious,  but  doubtless  requires  further  support  from  clinical 
and  pathological  observation. 

The  occurrence  of  perityphlitis  in  the  subjects  of  acute 
rheumatism  has  been  called  attention  to  by  Dr.  G.  A.  Suther- 
land in  a  paper  published  in  the  Edinburgh  Hospital  Reports  of 
1895. 1  Dr.  Sutherland  published  in  this  paper  examples  of 
this  association,  occurring  in  children,  in  whom  there  was  a 
personal  and  also  a  strong  family  history  of  rheumatic  fever. 
The  attacks  of  perityphlitis,  judging  from  the  reports,  were 
mild,  as  for  none  of  them  was  an  operation  required.  This  from 
the  strictly  scientific  aspect  detracts  necessarily  from  their 
value,  for  it  is  the  absolute  proof,  either  by  operation  or 
necropsy,  that  is  especially  desirable  in  a  question  of  such  a 
nature  as  this  one. 

We  have  quite  recently  met  with  a  case  resembling  in  some 
respects  those  described  by  Dr.  Sutherland,  and  for  leave  to 
use  the  notes  of  this  case  are  indebted  to  Dr.  W.  S.  Colman. 
A  boy,  aged  n,  was  admitted  in  August  to  the  Hospital 
for  Sick  Children,  Great  Ormond  Street,  for  rheumatic 
chorea.  The  chorea  was  not  severe  but  stubborn  ;  the  heart 
was  dilated,  and  there  was  a  faint  systolic  murmur.  While  in 
the  hospital  the  bowels  became  obstinately  constipated,  and 
pain  was  complained  of  in  the  right  iliac  fossa.  The  bowels,  in 
spite  of  treatment,  were  only  thoroughly  opened  upon  one  day 
between  August  14  and  22.  Synchronous  with  the  pain,  there 
was  a  rise  of  temperature.  The  fever  was  intermittent,  lasted 
for  about  fourteen  days,  and  reached  at  its  maximum  1010. 
The  tenderness  over  the  right  iliac  fossa  continued,  a  definite 
mass  could  be  felt,  and  vomiting  occurred  upon  two  occasions. 
The  bowels  were  kept  open  by  enemata,  and  gradually  the 
fever  and  internal  symptoms  disappeared. 

This  case  is  plainly  inconclusive,  for  all  the  symptoms  might 


IN  ASSOCIATION  WITH  PERITYPHLITIS       361 

have  been  the  results  of  constipation,  and  even  if  there  was,  as 
seemed  probable,  some  actual  appendicitis,  the  occurrence  of 
chorea  may  have  been  a  mere  coincidence. 

There  is,  we  believe,  a  general  agreement  among  those  who 
have  especially  studied  rheumatism  in  childhood,  that  such 
children  frequently  surfer  from  obscure  abdominal  pains.  Such 
experience  as  we  have  had  has  given  us  the  impression  that 
these  pains  are  generally  paroxysmal,  and  usually  referred 
above  the   umbilicus   to   the   epigastric  region.     They   have 


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interested  us,  because  it  has  seemed  difficult  to  explain  them 
satisfactorily,  though  it  is  probable  that  in  some  cases  the  pain 
is  situated  in  the  abdominal  muscles. 

The  occurrence,  in  association  with  perityphlitis,  of  multiple 
joint  affections,  having  the  character  of  a  rheumatic  arthritis, 
has  been  recorded  by  several  observers,  and  a  very  complete 
case  was  published  by  Dr.  Burney  Yeo  in  the  British  Medical 
Journaliov  June  16, 1894. 2  A  girl,  the  subject  of  an  acute  attack 
of  rheumatism  some  months  before,  had  been  ill  for  a  fortnight 
with  pains  in  the  elbows  and  knees  and  general  malaise.  She 
then  developed  severe  abdominal  pain,  and  was  admitted  upon 
April  16  to  King's  College  Hospital  with  a  definite  and  severe 
attack  of  perityphlitis.     There  was  temporary,  improvement. 


362  ARTHRITIS 

but  four  days  afterwards,  with  a  recrudescence  of  the  peri- 
typhlitis, her  elbows  and  wrists  swelled  and  became  extremely 
tender,  and  an  apical  systolic  murmur  present  on  admission 
became  louder  and  more  definite.  The  perityphlitis  was 
sufficiently  severe  to  raise  the  question  of  pysemic  metastases, 
but  complete  recovery  followed  without  operation.  The 
temperature  and  joint  lesions  reacted  to  a  marked  degree  to 
treatment  by  salicylates.  There  was  this  unusual  feature  about 
the  case  that  the  temperature  was  remarkably  high  and 
irregular  for  rheumatism,  reaching  on  one  occasion  105 °,  and 
on  another  over  1040,  but  it  must  be  allowed  that  there  was 
the  perityphlitis  also  to  be  reckoned  with.  Other  similar  cases 
have  been  reported  by  Sir  James  Grant,3  Dr.  Brazil,4  and  others, 
all  of  which  recovered,  some  with  marked  abatement  of  the 
symptoms  under  the  use  of  salicylates.  It  is  this  reaction  to 
salicylates  that  has  been  brought  forward  as  another  source  of 
evidence.  Their  value  has  been  commented  upon  by  Dr. 
Sutherland,  Dr.  Haig,5  Dr.  Beverley  Robinson,6  and  others, 
but  the  explanation  of  the  success  obtained  is  not  ascribed  by 
all  these  observers  to  the  same  cause.  Dr.  Haig,  looking 
upon  these  cases  of  appendicitis  and  arthritis  as  manifestations 
of  gout  rather  than  rheumatism,  considers  the  success  of  the 
salicylates  as  due  to  increase  in  the  elimination  of  uric  acid. 
Others  look  upon  their  success  as  evidence  of  the  rheumatic 
origin  of  the  illness.  Finally,  Dr.  Beverley  Robinson,7  though 
convinced  of  their  great  value  in  the  treatment  of  perityphlitis 
after  several  years  of  close  inquiry,  writes  as  follows  : 

"  I  do  not  remember  personally  to  have  seen  an  attack  of 
acute  articular  rheumatism  either  distinctly  precede  or  follow 
evident  signs  of  appendicitis,  and  to  be  connected  with  it  in 
such  a  way  that  the  relation  of  the  two  affections  was  clearly 
defined." 

The  inference,  we  think,  is  that  in  such  cases  as  these,  though 
salicylates  may  be  of  value  for  the  relief  of  symptoms,  their 
success  is  no  proof  of  the  rheumatic  character  of  those  symp- 
toms. This  is  a  view  maintained  by  several  authoritative 
writers,  and  in  this  paper  we  are  able  to  bring  forward  some 
evidence  in  its  support. 

To  recapitulate  at  this  point,  it  may  be  justly  said  that 
though  there  is  some  evidence  in  support  of  the  rheumatic 


IN  ASSOCIATION  WITH  PERITYPHLITIS       363 

origin  of  perityphlitis,  it  is  hardly  as  yet  sufficient  for  a  scientific 
proof,  and  the  possibility  of  coincidence  in  two  diseases  of 
common  occurrence  has  always  to  be  taken  into  account. 
During  the  two  years  that  one  of  us  was  medical  registrar  and 
pathologist  at  St.  Mary's  Hospital,  he  was  enabled  to  follow 
up  this  question,  especially  upon  the  clinical  side,  and  investi- 
gated sixty  cases  of  perityphlitis,  with  reference  to  this  question 
of  rheumatism.  As  his  guide  he  took  the  manifestations  of 
the  rheumatic  state  as  laid  down  by  Dr.  Cheadle  in  the 
Harveian  Lectures  for  1888,  and  the  observations  were  made 
upon  cases  of  every  grade  of  severity.  In  thirty-one  the 
diagnosis  was  confirmed  by  operation,  and  only  undoubted 
examples  were  chosen  ;  forty  were  first  attacks,  the  remainder 
were  recurrent,  and  eighteen  of  these  patients  were  subject  to 
repeated  relapses,  so  that  all  the  types  of  this  disease  were 
represented.  The  ages  varied  from  6  to  57  years.  In  none  of 
these  cases — and  this  is  in  agreement  with  Dr.  Beverley 
Robinson — could  he  trace  any  connection  between  the  attack 
of  perityphlitis  and  an  attack  of  rheumatism,  though  in  a 
certain  number  there  was  a  history,  more  or  less  doubtful,  of 
a  previous  rheumatic  attack.  Thus,  in  eleven  cases  there  was 
a  family  or  personal  history,  and  in  five  a  personal  history.  In 
one  case  there  was  a  definite  systolic  murmur,  but  this  patient, 
in  addition  to  perityphlitis  and  a  previous  arthritis,  had 
suffered  from  typhoid  and  dysentery,  and  was  apparently 
susceptible  to  most  infections. 

There  were  in  the  series  two  cases  of  multiple  arthritis 
occurring  shortly  after  the  onset  of  perityphlitis. 

Two  papers,  one  by  Piard8  upon  "  Metastatic  Suppurations 
in  Connection  with  Appendicitis,"  and  one  by  Akerman  9  upon 
"  Experimental  Osteo-myelitis,"  seem  to  throw  light  upon  these 
difficult  cases. 

Dr.  Piard,  in  the  Paris  Archives  de  Medecine  in  1896,  though 
he  made  no  observations  upon  arthritis,  gave  numerous 
examples  of,,  visceral,  pleural,  and  intra-muscular  abscesses 
occurring  after  appendicitis,  and  emphasised  the  important 
clinical  fact  that  such  metastases  are  especially  liable  to  occur 
in  those  cases  in  which  the  local  evidences  of  perityphlitis  are 
absent  or  but  slightly  marked.  Akerman,  in  the  third  volume 
of  the  "  Archives  of  Experimental  Medicine,"  published  some 
interesting  results   obtained   by   intravenous  inoculations   of 


364  ARTHRITIS 

the  bacillus  coli  into  young  rabbits.  If  pure  cultures  were 
injected  of  sufficient  strength  to  allow  characteristic  lesions 
to  occur,  a  multiple  osteo-myelitis  developed,  and,  with  this, 
changes  in  the  neighbouring  joints.  Usually  the  fluid  within 
them  was  increased  and  varied  in  character  with  the  virulence 
of  infection.  It  was  sometimes  clear,  sometimes  turbid,  and 
sometimes  purulent.  In  several  instances  the  bacillus  coli 
was  demonstrated  in  these  joints.  The  condition  developed 
more  slowly  than  in  ordinary  suppuration. 

Again,  numerous  investigators101112  have  demonstrated  the 
importance  of  the  colon  bacillus  in  perityphlitis,  and  this 
organism  has  been  demonstrated  in  the  metastatic  visceral 
abscesses,  and  by  Sevestre  and  Gaston  in  the  joints  in  a  case 
of  polyarthritis  complicating  the  disease. 

It  is  not  surprising,  in  the  face  of  the  observations  of  Piard 
and  Akerman,  that  cases  of  polyarthritis  in  connection  with 
perityphlitis  may  appear  clinically  much  like  rheumatic 
arthritis.  There  may  be  no  definite  local  evidence  of  the 
original  focus,  possibly  only  a  vague  history  of  abdominal  pain 
with  vomiting.  The  swellings  of  the  joints  may  be  multiple, 
and  disappear  during  life,  the  fever  be  lowered  and  pain 
relieved  by  salicylates,  yet  after  death  a  gangrenous  appendix 
and  visceral  abscesses  may  be  found,  pointing  conclusively  to 
the  metastatic  origin  of  the  joint  infection.  Not  only  may 
there  be  effusion  into  the  joints,  but  also  into  the  tendon 
sheaths  in  their  neighbourhood,  and  around  the  epiphyses  of 
the  bones.  If  we  can  be  guided  by  Akerman's  experimental 
results,  the  disappearance  of  the  joint  effusion  during  life  may 
be  looked  upon  as  an  evidence  of  the  slight  virulence  of  the 
local  infections.  If  with  this  the  general  toxaemia  be  severe, 
then  there  will  be  death,  but  disappearance  of  the  joint 
swellings  prior  to  its  occurrence  ;  if  the  general  poisoning  be 
not  severe,  then  there  will  be  recovery,  with  a  condition  of 
multiple  arthritis  simulating  acute  rheumatism.  In  a  case  of 
this  kind  which  ended  fatally,  and  in  which  the  appendix  was 
gangrenous,  we  have  seen  marked  relief  from  the  use  of 
salicylates. 

It  is  probable,  therefore,  that  the  arthritis  occurring  in  con- 
nection with  perityphlitis  is  usually  of  the  nature  of  a  pyaemic 
rather  than  a  rheumatic  affection,  and  this  becomes  the  more 
probable  if  there  is  high  irregular  pyrexia,  or  if  there  are  rigors. 


IN  ASSOCIATION  WITH  PERITYPHLITIS       365 

That  the  condition  should  be  liable  to  occur  when  the  local 
indications  of  perityphlitis  are  slight,  is  in  part,  we  suppose, 
explained  as  follows  :  If  the  attack  is  very  severe,  there  is 
perforation,  with  either  speedy  death,  or  recovery  after  an 
immediate  operation.  If  the  attack  is  not  so  severe,  but  the 
local  signs  are  definite,  then,  should  unfavourable  symptoms 
arise,  a  laparotomy  is  at  once  performed,  and  the  metastases 
nipped,  as  it  were,  in  the  bud.  If,  however,  the  local  signs  are 
practically  absent,  and  the  history  of  the  illness  indefinite, 
then  these  metastases  develop  while  there  is  doubt  as  to  where 
the  primary  focus  is  to  be  found,  or  as  to  whether  such  a  focus 
exists  at  all.  It  is  probable  also  that  in  these  cases  there  is  an 
unusually  rapid  blood  infection,  rather  than  any  great  direct 
extension  of  the  local  suppuration. 

This  question  of  the  exact  nature  of  the  arthritis  is  clearly 
one  of  practical  moment,  for  if  rheumatic,  temporising  measures 
might  be  employed,  but  if  pysemic,  removal  of  the  local  focus 
is  imperative.  It  is  of  some  interest  that  just  as  this  arthritis 
may  closely  resemble  that  of  rheumatism,  so  may  rheumatic 
arthritis  sometimes  resemble  perityphlitis.  Upon  three 
occasions  we  have  seen  monarticular  rheumatism  of  the  right 
hip- joint  in  a  child  simulate  this  condition.  The  thigh  is 
flexed,  and  the  pain  radiates  over  the  right  iliac  fossa.  In 
these  days  of  active  surgery  the  diagnosis  is  of  course  important, 
and  usually  quite  easy.  Other  joints  become  affected,  or  the 
heart  shows  evidence  of  active  rheumatism,  indeed  the  know- 
ledge of  the  possibility  of  this  occurrence  is  usually  sufficient 
to  prevent  any  error.  In  conclusion,  it  appears  to  us  that 
clinical  evidence  is,  on  the  whole,  against  the  rheumatic  origin 
of  the  arthritis  associated  with  perityphlitis. 

REFERENCES 

1  Dr.  G.  A.  Sutherland,  "Appendicitis  and  Rheumatism,"  Lancet, 
August  24,  1895  '>  Edinburgh  Hosp.  Rep.,  1895. 

2  Dr.  Burney  Yeo,  "Rheumatic  Perityphlitis,"  Brit.  Med.  Jour., 
June  1 6,  1894. 

3  Sir  James  Grant,  New  York  Med.  Rec,  November  11,  1893, 
p.  609. 

*  Dr.  Brazil,  Brit.  Med.  Jour.,  May  1895. 

6  Dr.  A.  Haig,  Brit.  Med.  Jour.,  June  30,  1894. 

6  Dr.  Beverley  Robinson,  New  York  Med.  Rec,  1895,  p.  375. 

7  In  a  recent  letter  Dr.  Robinson  expressed  himself  as  convinced 


366  ARTHRITIS  WITH  PERITYPHLITIS 

from  clinical  observation  of  the  rheumatic  origin  of  some  cases  of 
appendicitis. 

8  E.  Piard,  "  Des  Suppurations  a,  distance  dans  l'appendicite,"  Arch, 
gen.  de  Med.,  Paris,  1896,  II. 

9  Akerman,  "  Lesions  Osteomyelitiques,"  Arch,  de  Med.,  exper.  No.  3. 

10  Hodenphyl,  "Etiology  of  Appendicitis,"  New  York  Med.  Jour., 

1893. 

11  Barbacci,  Centrl.  und  Allg.  Path,  ct  Path.  Anat.,  October,  1893. 

12  Macaigne,  Le  Bacterium  Coli  Commune,  son  role  dans  la  Pathologie, 
Paris,  1892. 


PAPER  NO.  XXV 

A  FURTHER  CONTRIBUTION  TO  THE  STUDY 
OF  RHEUMATISM.  THE  EXPERIMENTAL 
PRODUCTION  OF  APPENDICITIS  BY  THE 
INTRAVENOUS  INOCULATION  OF  THE 
DIPLOCOCCUS 

(Reprinted  from  the  Proceedings  of  the  Royal  Society  of  Medicine, 
191 1,  vol.  v,  Pathological  section,  pp.  18-29.) 

From  the  Research  Laboratories  of  University  College  Hospital 
and  the  Cancer  Hospital  Research  Institute. 

This  paper  records,  we  believe,  the  first  examples  of  an  experimental 
appendicitis  produced  by  the  diplococcus  isolated  from  a  lesion  of  acute 
rheumatism.  Such  results  naturally  revived  the  questions  considered 
in  the  previous  paper  concerning  the  association  of  rheumatism  and 
appendicitis,  and  although  the  greatest  caution  is  needed  in  drawing 
conclusions  from  experimental  investigations,  lends  support  to  the 
view  that  there  may  be  some  direct  connection.  Appendicitis  from  this 
standpoint  becomes  a  symptom  of  various  infections,  including  among 
these  the  rheumatic. 

The  experiment  which  by  intravenous  inoculation  produces  as  the 
only  obvious  lesion  of  the  entire  length  of  the  alimentary  canal  an 
appendicitis  is  a  very  striking  one,  and  reminds  us  that  the  solitary 
lesion  of  appendicitis  in  man  need  not  necessarily  be  the  outcome  of  a 
local  cause  within  the  lumen  of  the  tube,  but  may  result  from  an  infection 
gaining  access  from  the  peritoneal  surface  by  the  general  blood  stream. 
In  this  country  this  possibility,  in  spite  of  Kelynack's  early  work,  has 
been  somewhat  overlooked,  but  Adrian's  researches  in  Germany  in 
1902,  had  stimulated  this  line  of  inquiry  in  that  country,  where  a 
considerable  literature  has  arisen  around  the  question. 

The  first  step  in  this  communication  is  to  indicate  accurately 
the  source  of  the  infective  agent  with  which  our  results  were 
obtained. 

A  boy,  aged  14,  previously  healthy  and  with  a  good  family 
history,  came  to  University  College  Hospital  in  August  1911, 

367 


368  EXPERIMENTAL  PRODUCTION 

suffering  from  a  first  attack  of  acute  rheumatism  of  five  days' 
duration.  It  commenced  with  pain  in  both  knees  and  ankles, 
and  later  in  the  left  shoulder.  His  temperature  was  100.50  F., 
and  pulse-rate  100  to  the  minute.  Both  knee-joints  were 
tender  and  full  of  fluid,  and  the  other  joints  named  above  were 
painful.  For  twenty-four  hours  an  apical  systolic  murmur 
was  faintly  audible,  but  this  disappeared,  and  the  boy  made  a 
rapid  and  complete  recovery.  He  was  treated  with  salicylate 
of  soda.  The  only  point  at  all  unusual  in  this  case  was  the 
excess  of  fluid  in  both  knee-joints,  the  right  one  being  dis- 
tended. Mr.  C.  E.  Shattock,  acting  house  physician,  tapped 
this  joint  for  us  and  a  greenish  fluid,  which  coagulated  and 
contained  some  fibrinous  shreds,  was  obtained.  From  this 
the  diplococcus  was  isolated  and  grown  in  pure  culture,  and  is 
the  infective  agent  which  we  have  used  for  the  following 
experiments. 

The  animals  used  for  experimentation  were  rabbits,  and  we 
would  lay  special  stress  upon  the  point  that  we  used  con- 
sistently for  the  first  time  young  ones  of  some  six  to  seven 
weeks  of  age.  All  the  injections  were  made  from  bouillon 
cultures  into  the  auricular  veins. 

The  first  animal  injected  with  a  large  dose  died  of  general 
pericarditis.  The  second  was  six  weeks  old  and  received  \  c.c. 
of  a  bouillon  culture.  Multiple  arthritis  followed  and  mucous 
diarrhoea,  the  animal  dying  from  an  intussusception  of  some 
days'  duration.  In  passing  we  would  comment  upon  this 
occurrence  of  acute  intussusception  in  two  animals  as  a  sequel, 
and  possibly  a  result,  of  the  infection.  A  pure  culture  of  the 
diplococcus  taken  from  the  joint  of  this  animal  was  used  for 
the  third  rabbit.  This  was  seven  weeks  old,  and  was  inoculated 
on  September  2  with  1  c.c.  of  a  bouillon  culture.  Monarthritis 
of  the  left  knee-joint  developed,  with  general  illness  and 
diarrhoea  ;  death  occurred  on  the  third  day.  The  post-mortem 
showed  that  for  1%  in.  in  the  middle  two-fourths  of  the  appendix 
there  was  acute  inflammation.  The  left  knee-joint  showed  the 
usual  early  synovitis.  The  liver  showed  fatty  areas.  The 
spleen  was  slightly  enlarged  and  firm.  The  kidneys  were  not 
remarkable.  There  were  no  petechiae  and  there  was  no  post- 
mortem staining,  the  heart  was  not  opened,  but  there  was  excess 
of  fluid  in  the  pericardial  cavity.  The  diplococcus  was  recovered 
in  pure  culture  from  the  left  knee-joint  and  the  heart's  blood. 


FICr.   88 

Experimental  appendicitis  (rabbit).     Abdomen  opened,  showing-  the 

swollen  and  inliamed  appendix.     The  left  knee-joint  which  was  in  a 

condition  of  acute  arthritis,  has  been  opened. 


FIG.  89 


Experimental  appendicitis  (rabbit).     Section  through  the  inflamed  area  of  the  appendix,  showing' : 

1.  Exudation  in> lumen.     2.  Destruction   of  Lieberkiihn's  crypts.      3.  Necrosis  of  lymphoid  follicles. 

4.  Dilatation  of  blood-vessels  at  the  base  of  the  subnmeosa.     Cf.  Fig  98. 


II'..  f'O 

Experimental  appendicitis.     A  diagram  showing  ballooning  of  the 

I    i\.  the-  result  of  local  infection  of  the  wall  by  tlie  diplococcns. 


*&* 


^A 


FIG.    91 

Experimental  appendicitis  (rabbit).  Section  through  the  wall  of  the  appendix  >h..wing  the  formation 

of  an  ulcer. 


OF  APPENDICITIS  369 

The  appendix  was  clearly  inflamed  and  the  mucous  membrane 
swollen  and  red.  A  small  piece  was  excised  for  histological 
investigations. 

The  details  of  this  histological  examination  are  as  follows  : 
The  muscular  and  serous  coats  of  the  bowel  are  healthy, 
but  the  mucous  and  submucous  layers  show  extensive 
necrosis.  There  is  destruction  of  Lieberkuhn's  glands  and 
the  lymphoid  tissue.  The  basal  vessels  of  the  submucosa 
are  engorged  with  blood,  and  numerous  diplococci  can  be 
seen  both  in  the  vessels  and  in  the  tissues  of  the  mucous 
and  submucous  coats.  The  Bacillus  coli  has  invaded  the 
necrotic  area.  Lastly,  there  is  a  slight  hbrino-cellular  exuda- 
tion into  the  lumen  of  the  gut.  Although  this  was  the 
third  rabbit  aUuded  to  in  this  paper,  four  others  had  been 
inoculated  and  developed  multiple  arthritis  without  appen- 
dicitis. One  more  in  this  series,  however,  that  is,  the  fourth 
mentioned  here,  developed  in  addition  to  multiple  arthritis  in 
both  elbow-,  knee-  and  carpal- joints,  some  diarrhoea  and  was 
killed  when  in  extremis  on  the  fifth  day.  The  middle  two-fourths 
of  the  appendix  showed  small  opaque  areas,  deep  seated  in  the 
substance  of  the  wall,  and  this  part  was  swollen  and  firm  to 
the  touch.  The  blood-vessels  in  this  situation  were  engorged. 
On  opening  the  appendix  a  mucoid  faecal-stained  fluid  escaped, 
and  at  one  spot  on  the  inner  surface  a  reddened  depressed  area 
the  size  of  a  hemp  seed  was  visible.  The  opaque  areas  seen 
from  the  external  aspect  were  still  more  obvious  from  within  ; 
at  the  junction  of  the  appendix  with  the  caecum  there  was  an 
enlarged  lymphatic  gland,  and  there  was  excess  of  fluid  in  the 
peritoneal  cavity.  The  spleen  was  slightly  enlarged  but  not 
soft,  the  liver  was  dark  and  firm  and  the  kidneys  pale.  The 
heart  was  dilated  and  full  of  blood  ;  there  was  no  pericarditis  or 
endocarditis.  The  lungs  were  congested  and  there  was  excess 
of  fluid  in  the  pericardial  cavity.  A  pure  culture  of  the  diplo- 
coccus  was  recovered  from  a  knee-joint.  The  depressed  area 
in  the  appendix  proved  to  be  an  acute  ulcer,  the  histology  of 
which  was  as  follows  :  The  chief  changes  are  visible  in  the 
mucous  and  submucous  coats.  These  are  of  two  kinds,  in  some 
places  there  is  disappearance  of  the  lymphoid  tissue  with  a  ten- 
dency to  necrosis,  in  others  a  proliferation  of  the  connective- 
tissue  elements,  pointing  to  the  first  stage  towards  a  fibrosis. 
Diplococci  were  not  demonstrated  in  the  portion  of  the  tissue 

24 


370  EXPERIMENTAL  PRODUCTION 

examined,  in  which  reparative  processes  were  just  commencing. 
In  the  area  of  ulceration  there  is  local  necrosis  of  the  mucosa 
and  submucosa,  with  destruction  of  the  epithelium  of  Lieber- 
kiihn's  follicles  and  the  lymphoid  tissue.  The  muscular  and 
serous  coats  are  not  involved  and  formed  the  base  of  the 
ulcer.  The  connective  tissues  bounding  the  necrotic  area 
show  commencing  proliferation. 

Another  series  of  inoculations  was  made  from  the  culture 
taken  from  the  first  rabbit  which  had  suffered  from  acute 
appendicitis,  and  one  of  this  series  was  killed  when  in  extremis 
on  the  third  day.  During  life  arthritis  of  both  knee-joints 
had  shown  itself  and  there  was  some  diarrhoea  with  general 
illness,  the  result  of  the  inoculation.  On  opening  the  abdomen 
a  condition  was  observed  which  we  must  ask  you  to  accept 
from  our  account,  because  in  the  process  of  preservation  it 
could  not  be  preserved.  We  have  illustrated  it  by  means  of  a 
diagram.  The  middle  two-fourths  of  the  appendix  were  ballooned 
and  in  the  walls  were  small  opaque  areas  not  so  extensive  as 
in  the  preceding  case,  and  situated  chiefly  along  the  mesenteric 
attachment.  The  viscera  showed  no  noteworthy  features 
and  both  knee-joints  were  in  a  condition  of  early  arthritis. 
The  diplococcus  was  recovered  from  one  of  these  in  pure 
culture.  The  histology  of  this  condition  shows  the  earliest 
stage  of  an  infection  by  the  blood  stream.  The  first  changes 
appear  in  the  mucous  and  submucous  layers,  but  chiefly  in  the 
lymphoid  follicles  of  the  latter.  Small  foci  of  polynuclear  cells 
can  be  seen  here  and  there  surrounding  the  minute  blood 
capillaries,  and  every  stage  of  inflammatory  change  can  be 
traced  up  to  complete  destruction  of  the  normal  tissue,  ending 
either  as  necrosis  or  connective- tissue  proliferation.  Diplococci 
are  visible  in  various  stages  of  destruction  within  the  phagocytic 
cells,  according  to  the  stage  of  inflammatory  reaction. 

The  last  series  that  have  been  inoculated  consisted  of  three 
young  rabbits  seven  weeks  old,  which  were  intravenously 
injected  on  October  6  with  very  small  doses  (0.25  c.c.  and 
0.1  c.c.)  of  a  bouillon  culture  from  the  knee-joint  of  the  pre- 
ceding rabbit  with  appendicitis.  All  suffered  from  arthritis, 
and  one  from  diarrhoea,  and  this  one  died  on  the  ninth  day. 
There  was  marked  arthritis  of  the  left  carpal  joint  and  slight 
of  both  knee-joints,  the  synovial  membranes  of  which  were  red 
and  congested.     About  \  oz.  of  turbid  fluid  was  removed  from 


FIG.  92 

The  earliest  visible  change  in  experimental  appendicitis  (rabbit"). 

About  the  middle  third  is  seen  a  pale  area  surrounded  by  congested 

vessels  :  the  pale  area  is  the  result  of  tissue  necrosis. 


FIG.  93 

Experimental  appendicitis  (rabbit).    Section  through  the  wall  of  the  appendix  under  low  magnifica- 
tion   showing"   the    early  stage.     Lieberkiikn's   crypts    are    not   damaged,  but  areas  of   necrosis  are 
visible  in  the  lymphoid  follicles  of  the  submucosa. 


Experimental  appendicitis.   Section  through  a  part  of  the  wall  of  the 

appendix,  showing  necrosis   of  lymphoid   tissue  and  perivascular 

exudation. 


OF  APPENDICITIS  371 

the  peritoneal  cavity,  and  the  serous  membrane  showed  early 
inflammatory  changes.  The  appendix  at  the  junction  of  the 
last  fourth  with  the  first  three-fourths  showed  an  opaque  area 
deeply  seated  in  its  walls.  The  blood-vessels  were  congested. 
As  regards  the  other  viscera  there  was  no  noticeable  feature 
except  that  the  spleen  appeared  to  be  unusually  small.  Cul- 
tures from  the  left  carpal  joint  and  peritoneal  fluid  gave  a  pure 
growth,  and  films  also  showed  the  diplococci.  We  would 
emphasise  the  absence  of  the  Bacillus  coli  in  the  films  and 
cultures  of  the  peritoneal  fluid.  Thus  it  will  be  recognised 
that  in  this  case,  which  had  lasted  nine  days,  some  peritonitis 
had  occurred  and  the  living  micrococci  were  present  in  the 
peritoneal  fluid. 


Summary 

To  summarise  our  histological  results,  we  would  point  out 
the  occurrence  of  (1)  a  very  early  appendicitis,  (2)  a  very 
severe  appendicitis,  and  (3)  the  formation  of  an  ulcer  as  the 
result  of  a  local  deposit  of  the  diplococcus  intravenously 
injected.  We  would  also  express  our  belief  that  in  human 
appendicitis,  apart  from  the  complicating  event  of  a  concretion 
which  we  know  is  not  a  constant  occurrence — the  histological 
changes  might  be  well  explained  by  our  results.  The  early 
cases  with  their  deposits  in  the  submucosa  and  mucosa  showing 
cell  proliferation  and  little  necrosis,  might  well,  if  they  had 
been  prolonged  in  duration,  have  produced  sclerosis  of  the  wall 
such  as  occurs  in  chronic  human  appendicitis.  The  acute  case 
with  much  necrosis  would  represent  the  virulent  human 
condition.  Lastly,  the  ulcer,  had  it  healed  and  been  rather 
more  extensive,  would  have  produced  the  stricture  so  often 
seen  in  man. 

The  rapid  destruction  of  the  diplococci  by  the  tissues  is  a 
most  interesting  event,  fully  bearing  out  our  previous  experi- 
ences as  to  this  micrococcus,  which  have  led  us  so  repeatedly 
to  explain  the  difficulty  of  its  isolation  during  life. 

The  enlargement  of  the  lymphatic  gland  at  the  base  of  the 
appendix  is  paralleled  in  human  appendicitis. 

In  none  of  these  cases  or  in  the  twenty-four  rabbits  inoculated 
in  this  research  was  there  a  single  abscess  in  the  viscera.  In 
so  far  as  these  results  are  the  outcome  of  infection  with  a 


372  EXPERIMENTAL  PRODUCTION 

micro-organism  obtained  during  life  from  rheumatic  arthritis, 
and  a  micro-organism,  too,  capable  of  reproducing  a  similar 
arthritis,  they  are,  we  believe,  a  new  contribution  to  the 
subject  of  experimental  medicine  and  a  new  fact  in  the  patho- 
logy of  the  important  condition  of  appendicitis.  If,  however, 
we  were  to  claim  that  the  wider  question  of  the  possibility  of 
appendicitis  arising  as  a  local  result  of  a  general  blood  infection 
had  not  been  realised  and  experimentally  investigated  before, 
then  we  should  do  a  gross  injustice  to  others.  Absolutely 
independent  as  these  investigations  of  ours  have  been,  we  must 
refer  to  Adrian's  paper  published  ten  years  ago  upon  the 
occurrence  of  appendicitis,  both  clinical  and  experimental,  as 
a  result  of  general  infection.  This  author,  in  a  masterly 
investigation,  refers  to  this  production  of  appendicitis  in 
rabbits  by  the  intravenous  injection  not  only  of  streptococci, 
but  also  staphylococci,  typhoid  bacilli,  pneumococci,  and  the 
Bacillus  coli.  In  the  investigation  with  the  pneumococcus  he 
demonstrated  the  micrococcus  in  the  wall  of  the  appendix, 
and  his  microscopic  section  of  the  inflamed  appendix 
resulting  from  a  streptococcus  infection,  the  figure  of 
which  is  in  accord  with  the  histological  results  that  we 
have  shown.  He  gave  no  details  of  the  formation  of  an 
ulcer,  or  of  another  lesion  such  as  arthritis,  or  of  the  condi- 
tion of  the  peritoneal  fluid,  nor  does  he  mention  the  source  of 
the  streptococcus,  but  these  points  are  of  secondary  importance 
with  regard  to  the  general  question  with  which  his  contribution 
was  concerned. 

In  his  paper  Adrian  gives  many  references  to  the  work  of 
others  upon  the  general  question  of  the  origin  of  appendicitis 
from  a  general  blood  infection  or  local  injury.  Roux  and 
Josue,  Roger,  Beauserrat,  de  Rouville,  Gouget,  and  others 
have  investigated  in  various  ways  upon  this  question  and 
Adrian's  paper  in  the  Mitteilungen  aus  den  Grenzgebieten  der 
Medizin  und  Chirugie,  1901,  vii,  p.  407,  reviews  this  work. 
We  would  make  the  following  concluding  observations  : 
(1)  There  seems  to  us  no  doubt  that  in  these  cases  acute 
appendicitis  resulted  directly  from  an  intravenous  inoculation 
of  a  diplococcus  obtained  during  life  from  an  acute  rheumatic 
arthritis,  and  it  appeals  to  us  as  interesting  that  it  was  the  only 
obvious  alimentary  lesion,  a  point  which  Adrian  noted  in  his 
cases. 


feSpyOt:  mlKm 


fig.  95 

Experimental  appendicitis  (rabbit).  Section  through  the   inflamed 

area  showing-  destruction  of  the  diplococci  within  the  tissue-cells. 

Cf.  Fig.  102. 


# 


o 


# 


*         a 


^ 


FIG.   96 


JAFORD*^- 


Experimental  appendicitis.    Section  through  an  inflamed  area  in  the  mucous 
membrane  showing'  the  diplococci. 


FIG.  97 
Experimental  appendicitis  Section  showing  dlplococci  in  a  lil i-vessel  of  the  submucosa. 


OF  APPENDICITIS  373 

(2)  The  conditions  that  were  produced  were  of  varying 
severity. 

(3)  In  each  case  the  animal  was  young  ;  heretofore,  we  have 
not  observed  such  a  condition  in  the  older  animals.  This  may, 
or  may  not,  prove  to  be  an  accurate  observation. 

(4)  The  condition  arises  without  the  presence  of  any  con- 
cretion or  foreign  body  in  the  appendix  and  commences  deep 
in  the  wall  of  the  appendix.  This  militates,  in  our  opinion, 
against  the  view  held  by  Aschoff  that  in  human  appendicitis 
this  disease  starts  within  the  lumen  of  the  appendix. 

(5)  It  is  interesting  that  the  middle  part  of  the  length  of 
the  appendix  is  affected,  a  position  in  which  a  stricture  is  so 
often  found  in  man. 

(6)  In  one  case  early  peritonitis  with  living  diplococci  in 
the  peritoneal  fluid  occurred,  although  there  was  no  perfora- 
tion— a  point  of  much  importance  in  its  bearing  upon  the 
pathology  of  human  appendicitis. 

(7)  The  ballooning  of  the  affected  area  of  the  appendix  in 
one  case  suggests  the  probability  that  in  man  some  such  loss 
of  tone  favours  stagnation  of  secretions  and  contents,  and  the 
formation  of  a  concretion. 

(8)  The  association  of  arthritis,  mucous  diarrhoea  and 
appendicitis  is  of  interest  in  its  bearing  upon  the  difficult 
question  of  auto-intoxication .  from  the  bowel  in  the  human 
subject  as  a  cause  of  arthritis.  It  suggests  that  rather  than 
this  being  the  primary  factor,  the  probability  is  that  all  the 
lesions  may  be  the  result  of  some  primary  cause  circulating  in 
the  blood  stream  and  determining  to  these  various  positions. 

(9)  We  do  not  assert  for  one  moment  that  the  only  cause  of 
appendicitis  is  this  diplococcus.  Adrian's  investigations  and 
those  of  others  are  sufficient  evidence,  quite  apart  from  clinical 
experience,  to  prevent  us  falling  into  this  error. 

(10)  Whether  or  not  these  results  favour  the  widely  held 
view  of  a  relationship  between  acute  rheumatism  and  appen- 
dicitis must  depend  upon  the  significance  that  is  attached  to 
this  diplococcus  and  the  degree  of  parallelism  that  exists 
between  human  disease  and  experimental  infection. 


PAPER  NO.  XXVI 

A  FURTHER  CONTRIBUTION  TO  THE  STUDY 
OF  THE  .ETIOLOGY  OF  APPENDICITIS 
AS  A  RESULT  OF  A  BLOOD  INFECTION; 
WITH  PARTICULAR  REFERENCE  TO  THE 
TONSILS  AS  THE  PRIMARY  SEAT  OF 
INFECTION 

(Reprinted  from  the  Lancet,  August  17,  1912) 

This  short  paper  brings  again  into  prominence  the  possibility  of 
appendicitis  arising  as  a  blood  infection  from  a  distant  focus.  In  this 
case  the  primary  lesion  was  apparently  a  streptococcal  tonsillitis.  The 
illustrations  of  this  paper  hitherto  unpublished,  should  be  compared 
with  those  in  the  preceding  one,  and  the  similarity  of  the  human  and 
experimental  lesions  will  be  seen  to  be  most  striking. 

In  this  communication  we  shall  attempt  to  advance  toward  a 
practical  issue  the  suggestions  that  we  put  forward  as  a  result 
of  some  experimental  investigations  reported  in  the  Lancet 
last  year.1 

1.  The  Case 

The  case  upon  which  our  new  facts  are  based  was  that  of 
a  girl,  aged  15  years,  who  was  taken  to  University  College 
Hospital  on  June  2,  1912,  suffering  from  a  first  attack  of 
appendicitis.  The  illness  was  a  very  definite,  but  not  unusually 
severe  one,  and  the  diagnosis  was  particularly  easy  because 
in  addition  to  the  ordinary  signs  of  the  disease  the  enlarged 
and  tender  appendix  could  be  easily  felt  through  the  abdominal 
wall.  The  duration  of  the  attack  was  forty-eight  hours.  To 
Mr.  H.  C.  G.  Pedler,  the  house  physician,  we  were  indebted 
for  the  interesting  and  valuable  observation  that  the  right 
tonsil  was  inflamed,  and  in  some  of  the  crypts  a  follicular 
deposit   was    evident.     No    complaint    of   a   sore-throat    had 

374 


FIG. 


Section  of  tbe  acutely  inflamed  appendix  (human),  under  a  low  power  (cf.  Fig.  89),  showing:  1.  Exudation  in 

lumen.      2.  Destruction  of  Lieberkiikn's  crypts.      3.  Xeerosis  of  lymphoid  follicles.      4.  Fibrino-cellular 

exudation  at  tbe  base  of  the  subniucosa.     5.  The  inflamed  serous  membrane. 


.♦*. 


.'.  n? 


•.•v:..*'.i-.:y**iV.-Vv,,t..^   %* 


as : .•-. 


»*       H 


*         *  •*  Nib  * 


:   ■;•••.; ,-  :•  •*•  ;•;  ■  'A •.':■* .->     ■; :r.  .--*;■.      ;**    ,.  v 


I'll,.    9i 


\  nut  her  part  of  the  same  sectionshown  in  the  preceding  figure  under 

a   higher  power,  showing  infiltration   of  the  muscular  coat-   with 

inflammatory  exudation  and  dilatation  of  the  vessels,  with  fihrino 

cellular  exudation  in  the  serous  membrane. 


AETIOLOGY  OF  APPENDICITIS  375 

been  made  by  the  patient,  who  was  no  doubt  suffering  far 
more  from  abdominal  pain.  Mr.  Raymond  Johnson  operated 
at  once  and  removed  a  large  and  swollen  appendix  covered 
with  fibrino-plastic  exudation.  There  was  neither  gangrene 
nor  perforation,  and  there  was  no  concretion.  The  patient 
made  an  uninterrupted  recovery.  There  was  no  previous 
history  of  any  serious  illness. 

2.  The  Investigation 

While  under  the  anaesthetic  a  culture  was  taken  from  the 
right  tonsil,  and  the  appendix  was  placed  in  a  sterile  tube. 

(a)  The  bouillon  culture  from  the  throat  showed  mainly 
strepto-diplococci,  but  also  a  few  staphylococci  and  an 
occasional  bacillus.  There  was  no  difficulty  in  isolating  the 
diplococcus  from  the  culture. 

(b)  Cultures  from  the  appendix  made  by  smearing  the 
exudate  upon  agar  showed  mainly  the  bacillus  coli,  but  also 
some  colonies  of  strepto-diplococci. 

(c)  Cultures  from  the  sanious  fluid  which  had  exuded  from 
the  appendix  after  it  had  remained  a  few  hours  in  the  sterile 
tube  at  room  temperature,  and  which  had  been  then  withdrawn 
and  incubated  in  a  Pasteur  pipette,  gave  a  pure  culture  of 
strepto-diplococci . 

(d)  Some  of  the  sanious  fluid  inoculated  upon  agar  and  into 
bouillon  showed  strepto-diplococci,  but  a  predominance  of  the 
bacillus  coli. 

These  results  with  the  sanious  fluid  are  of  interest  because 
they  bear  out  our  experience  that  in  media  such  as  bouillon, 
devoid  of  immune  factors,  the  more  saprophytic  coli  organisms 
rapidly  get  the  upper  hand,  but  in  the  blood  serum  the  more 
pathogenic  organism  grows  the  more  readily.  This  point  as 
to  the  importance  of  serum  Kretz  had  already  dwelt  upon  in 
his  paper.2 

The  diplococci  from  the  throat  and  from  the  sanious  fluid  ap- 
peared to  us  morphologically  and  in  cultural  characters  identical. 

A.  Experimental  results  with  the  culture  from  the  throat.  The 
diplococcus  produced  arthritis  with  the  usual  accompanying 
symptoms  in  the  rabbits  intravenously  inoculated  and  was  again 
recovered  in  pure  culture  from  the  arthritic  exudations.  Later 
investigations  have  resulted  in  the  production  of  malignant 
endocarditis  with  infarctions  in  the  spleen  and  kidneys. 


376  ETIOLOGY  OF  APPENDICITIS 

B.  Experimental  results  with  cultures  from  the  sanious  fluid. 
Two  groups  of  investigations  were  made  :  (i)  Six  adult 
rabbits  were  inoculated  intravenously  with  subcultures  in 
bouillon  with  negative  result.  This  loss  of  virulence  in 
bouillon  is  a  frequent  event  in  the  cultivation  of  micrococci 
of  the  streptococcal  group.  (2)  Six  young  rabbits  of  six 
weeks  of  age  were  inoculated  from  subcultures  on  blood  agar. 
Of  these  animals  the  first  suffered  from  malaise  and  diarrhcea 
for  three  days  and  on  the  fourth  developed  arthritis  of  the 
right  shoulder-joint.  It  was  killed  on  the  eighth  day.  The 
diplococcus  was  recovered  from  the  inflamed  joint.  The 
spleen  was  small  and  the  other  organs  were  healthy.  The 
second  animal  developed  arthritis  of  both  knee-joints  on  the 
third  day  with  fever  and  malaise.  It  was  killed  on  the  fifth 
day.  The  post-mortem  examination  showed  arthritis  and 
appendicitis.  The  appendix  showed  the  middle  third  as  the 
injured  part,  and  there  were  necrotic  areas  in  the  deeper 
layers  of  the  wall  of  the  appendix  precisely  similar  to  those 
detailed  and  illustrated  by  us  in  our  paper  read  before  the 
Pathological  Section  of  the  Royal  Society  of  Medicine  in 
October  1911.  The  diplococcus  was  recovered  in  pure 
culture  from  the  joints.  The  third  rabbit  developed  arthritis 
of  the  left  knee-joint  on  the  third  day  and  was  killed  on  the 
fifth  ;  save  for  the  arthritis  it  was  apparently  healthy.  The 
fourth  rabbit,  after  transient  malaise,  recovered  without  any 
local  lesion.  The  fifth  rabbit  developed  arthritis  of  the  right 
knee-joint  on  the  third  day.  The  sixth  rabbit  developed 
multiple  arthritis  and  was  killed  on  the  fifth  day.  Thus  five 
out  of  the  six  rabbits  developed  arthritis  and  one  of  these  in 
addition  appendicitis.3 

Pathological  Investigations 

The  experimental  appendicitis  needs  no  further  description, 
for  it  resembled  precisely  the  condition  which  we  fully  described 
and  illustrated  in  1911. 

The  appendix,  however,  from  the  patient  deserves  some 
detail  in  description.  Sections  showed  an  acute  diffuse  change 
mainly  affecting  the  submucous  and  mucous  coats  and  the 
serous  covering  of  the  bowel.  The  submucous  and  mucous 
coats  were  in  a  state  of  acute  necrosis,  the  result  of  minute 
haemorrhages  from  and  thrombosis  of  the  vessels  in  the  sub- 


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FIG.  100 


Human  appendicitis.     Section  through  the  serous  membrane,  showing  diplococci  and 
inflammatory  exudation.     (Zeiss,  obj.  3  mm.,  apo.  oc.  ]  2.) 


'    •   •  '.    * ■».  •  !.'.:  v'~    :;    vi..  ;»*.'■■■'.'■, •••'•''    v  .'••■•:•  '-■     ',.'■'•''  '';'i'-'.   •. '  '■ '    •'  .. 

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-u*  *|;>- y'*;^':  vV! ^l5 '••-#%:  ■■-.'":  * '  '     ^\^*" 


FIG.   101 

A  ]);irt  oi  the  same  section  shown  in  Fig-.  98  under  higher  magnifica- 
tion, showing  necrosis  of  the  mucous  membrane  and  thrombosis  of 
vessels  with  fibrino-cellular  exudation  in  the  submucosa. 


^ETIOLOGY  OF  APPENDICITIS  377 

mucosa.  A  fibrino-cellular  exudation  infiltrated  the  sub- 
mucous coat,  in  which  the  lymphoid  tissue  was  almost 
completely  destroyed.  The  mucous  membrane  was  infiltrated 
with  inflammatory  cells,  and  there  was  almost  complete 
destruction  of  its  epithelial  covering  and  of  Lieberkiihn's 
glands,  only  a  slight  trace  of  the  deeper  crypts  being  visible. 
The  muscular  coat  was  also  infiltrated  with  inflammatory  cells 
and  the  greatly  swollen  serous  layer  was  cedematous  and 
infiltrated  with  fibrino-cellular  exudation.  Diplococci  were 
demonstrated  in  the  submucous  and  mucous  membranes,  but 
wrere  most  numerous  and  easily  demonstrated  in  the  serous 
membrane .  The  bacillus  coli  had  invaded  the  necrotic  tissue 
and  serous  covering  of  the  bowel.  The  condition  of  this 
human  appendix  was  a  counterpart  of  that  found  in  the  rabbits 
with  appendicitis,  as  illustrated  by  us  last  year. 

We  think  that  this  investigation  brings  us  a  step  forward 
in  the  study  of  the  aetiology  of  appendicitis.  Since  Kelynack  4 
in  1893  directed  our  attention  to  the  relation  of  tonsillar 
inflammation  to  appendicitis  many  German  investigators 
have  devoted  much  attention  to  the  point.  Our  earlier  paper 
showed  that  in  young  rabbits  a  micrococcus  which  we  look 
upon  as  the  exciting  cause  of  acute  rheumatism  could  produce 
a  local  lesion  in  the  appendix  by  direct  blood  infection,  and 
bearing  in  mind  the  importance  of  tonsillar  inflammation  in 
rheumatism  those  results  naturally  strengthened  the  view 
put  forward  by  Kelynack.  This  investigation  takes  us  forward, 
because  it  would  seem  beyond  reasonable  doubt  that  the 
diplococcus  in  the  tonsil  and  in  the  sanious  fluid  from  the 
appendix  were  identical  in  nature  and  the  cause  of  the  lesions 
in  the  human  throat  and  appendix  and  also  of  those  in  the 
appendix  and  joints  of  the  rabbits.  In  other  words,  it  seems 
to  prove  almost  conclusively  that  a  cause  of  appendicitis  may 
be  a  streptococcal  invasion-  through  the  blood  stream  from  a 
follicular  tonsillitis. 

REFERENCES 

1  Lancet,  October  28,  191 1,  p.  1189. 

2  "  Ueber  die  /Etiologie  der  Appendizitis,  Verhandlungen  der 
Deutschen  pathologischen  Gesellschaft,"  April  1910. 

3  A  seventh  rabbit  developed  arthritis  and  appendicitis  after  the 
publication  of  this  paper. 

4  "The  Pathology  of  the  Vermiform  Appendix";  London,  H.  K. 
Lewis,  1893. 


PAPER  NO.  XXVII 

OBSERVATIONS  UPON  APPENDICITIS  BASED 
UPON  A  COMPARATIVE  STUDY  OF  THE 
MORBID  ANATOMY  IN  THE  HUMAN  AND 
EXPERIMENTAL  DISEASE 

April  1913 

In  this  paper  the  method  adopted  for  isolating  the  streptococcus  from 
cases  of  streptococcal  appendicitis  is  detailed,  and  a  further  study  of 
the  morbid  changes  in  recurrent  human  appendicitis  has  been  added 
which  supports  the  view  that  in  such  cases  the  cause  is  an  infection 
attacking  the  organ  from  the  general  blood  stream.  Some  general 
observations  are  added  upon  the  pathology  of  the  disease. 

Since  our  papers  published  in  1911  and  1912,  upon  experi- 
mental appendicitis  produced  by  a  blood  infection  we  have 
investigated  more  closely  the  morbid  anatomy  of  the  disease 
in  man  with  the  object  of  comparing  the  lesions  with  those 
produced  by  experiment.  In  this  way  we  hoped  to  throw 
some  more  light  upon  the  origin  of  the  disease  in  man  as  the 
outcome  of  a  blood  infection  rather  than  of  a  direct  invasion 
by  micrococci  from  within  the  lumen,  or  of  injury.  A  very 
interesting  and  valuable  monograph  by  Kretz  has  convinced 
us  that  in  Germany  much  attention  has  been  directed  to  this 
subject.  In  this  country,  however,  the  published  writings  of 
more  recent  date  have  paid  but  little  attention  to  this  method 
of  origin. 

Quite  apart  from  the  possible  rheumatic  causation  of 
appendicitis  it  is  clear  that  if  the  disease  arises  by  infection 
from  the  general  blood  stream  such  hypothetical  causes  as 
faults  in  common  articles  of  diet,  sedentary  habits  and  con- 
stipation, and  foreign  bodies  must  take  a  very  secondary 
position.  On  the  other  hand,  if  the  research  recorded  in  the 
preceding  papers  should  meet  with  further  support,  and  we 

378 


t., 


*d 


"•^'i 


FIG.  102 

Human  appendicitis.     Section  through  the  submucosa  showing-  destruction  of  diplococci  in  the 
phagocytes.     (Cf.  Experimental  appendicitis.  Fig.  95.)     (Zeiss,  obj.  3  mm.,  Apo.  oc.  12.) 


OBSERVATIONS  UPON  APPENDICITIS  379 

may  add  that  in  Germany  many  clinical  observers,  for  example, 
Braun,  Kretz,  Krauss  and  Albrecht,  attach  the  greatest 
importance  to  tonsillar  infection,  it  is  clear  that  all  causes 
encouraging  angina  faucium  would  favour  its  incidence. 

It  would  be  premature  to  attempt  to  give  a  decided  opinion 
upon  the  role  of  a  tonsillar  infection  with  the  amount  of  exact 
evidence  before  us,  but  it  is  an  interesting  thought  arising 
out  of  this  possibility  as  to  whether  the  increase  in  the  disease 
which  some  are  confident  has  occurred  in  recent  years  may 
not  be  dependent  upon  the  great  wave  of  influenza,  an  affection 
which  so  frequently  commences  with  a  sore  throat.  Some 
authorities,  such  as  Lexer,  Klenk  and  Fried] ting,  although 
not  prepared  to  admit  a  tonsillar  infection  in  the  sporadic 
cases  are  inclined  to  this  when  small  epidemics  have  arisen  ; 
and  it  is  clear  that  in  the  future  a  careful  consideration  of 
the  whole  subject  is  worthy  of  close  attention  in  this  country. 
We  would  add  in  agreement  with  others  that  it  should  be 
remembered  that  the  abdominal  symptoms  in  appendicitis  are 
often  so  severe  as  to  make  the  patient  forgetful  of  any  previous 
sore  throat  of  slight  severity,  and  the  paramount  importance 
of  the  abdominal  diagnosis  distracts  the  attention  of  the 
medical  man  from  what  might  well  seem  a  trivial  occurrence. 

No  one,  we  believe,  would  for  a  moment  accept  that  the 
aetiology  of  appendicitis  Was  to  be  explained  as  invariably 
the  result  of  infection  from  the  tonsils,  for  it  is  certain  that 
in  many  cases  no  convincing  evidence  of  such  an  infection 
is  forthcoming,  and  although  there  is  no  theoretical  need  for 
the  tonsils  to  be  grossly  inflamed  in  order  to  allow  of  such 
infection  we  should  naturally  hesitate  to  assume  this  source 
without  some  decided  evidence  in  its  favour. 

At  this  point  we  would  emphasise  a  difficulty  in  the  investi- 
gation of  the  bacteriology  of  appendicitis,  which  not  only 
baffled  us  for  many  months,  but  which  is  a  very  real  one.  The 
isolation  of  the  micro-organisms  is  an  undertaking  full  of 
difficulty  and  involving  much  labour  because  the  bacillus  coli 
quickly  overgrows  the  streptococci  which  are  so  often  the 
pathogenic  cause. 

We  do  not  affirm  that  the  bacillus  coli  may  not  be  a  cause 
of  appendicitis,  but  we  are  of  opinion  that  it  is  more  usually  a 
saprophyte  which  bewilders  us  by  overgrowing  our  culture 
media.     On  this  account  we  found  it  necessary  to  adopt  a 


380  OBSERVATIONS  UPON  APPENDICITIS 

special  technique  of  the  following  nature.  Our  material  has 
consisted  of  appendices  obtained  directly  after  removal  by 
the  surgeon.  In  the  amputation  the  efferent  lymphatics 
which  drain  from  the  mucous  and  serous  coats  into  the 
mesentery  are  cut  across,  and  we  receive  the  appendix  into  a 
sterilised  tube  containing  no  culture  medium.  This  we 
keep  in  the  cool  for  some  hours.  The  fluid  oozing  out  is 
blood  stained  and  collects  at  the  bottom  of  the  tube.  Then  this 
fluid  is  withdrawn  in  a  Pasteur  pipette,  the  end  of  which  is 
sealed  off  in  the  flame,  and  incubated  for  twelve  to  twenty-four 
hours  at  the  body  temperature.  If  the  case  is  an  early  one, 
the  pathogenic  agent  is  found  sometimes  in  pure  culture, 
sometimes  with  a  poor  growth  of  the  bacillus  coli  from  which 
it  can  be  separated  with  comparative  ease. 

It  was  extremely  interesting  to  us  to  find  that  Kretz  had 
in  his  monograph  suggested  that  a  fluid  of  this  kind  might  be 
the  best  medium. 

All  our  later  experiences  have  pointed  to  a  streptococcus 
as  the  most  frequent  cause  of  appendicitis,  and  it  is  with  this 
that  we  have  produced  experimental  results.  Further  the 
streptococcus  is  extremely  likely  to  produce  polyarthritis  in 
rabbits,  in  fact  this  result  in  young  rabbits  (the  only  ones  in 
which,  so  far,  we  have  produced  appendicitis)  has  been  almost 
constant.     Endocarditis  has,  however,  also  resulted. 

These  experiences  have  borne  out  the  results  of  other 
investigators  in  so  far  that  they  also  have  frequently  isolated 
a  streptococcus,  and  they  have  also  extended  them  by  com- 
pleting the  experimental  evidence  which  had  been  previously 
incomplete.  Other  micrococci  have  been  isolated  as,  for 
example,  pneumococci  and  staphylococci,  and  twelve  years 
ago  Adrian  demonstrated  that  appendicitis  might  be  produced 
experimentally  by  intravenous  inoculation  of  rabbits  with 
various  micrococci. 

The  question  arises,  and  has  not  yet  been  answered,  *as  to 
the  nature  of  these  streptococci  which  would  seem  to  be  the 
most  frequently  occurring  infection. 

Our  first  paper  in  which  the  diplococcus  rheumaticus  was 
isolated  from  the  inflamed  knee-joint  during  life  makes  it 
reasonable  to  entertain  the  view  that  among  these  streptococci 
the  rheumatic  infection  may  have  a  place.  If  then,  in  the 
future,  among  the  causes  of  appendicitis  acute  rheumatism 


FIG.  103a 


FIG.    103b 


Transverse  sections  of  two  appendices  (human).  These  semi-dia- 
grammatic drawings  were  made  under  low  magnification.  Fig.  103a 
was  taken  from  a  normal  appendix.  Fig.  103b  is'fromacaseof  recurrent 
appendicitis  in  a  man  aged  28  ;  perforation  occurred  in  the  last 
attack.  Showing  the  destruction  of  the  deeper  parts  of  Lieberkiilm's 
follicles  and  the  lymphoid  erypts  of  the  subniucosa  which  are 
replaced  by  fibrous-tissue  formation.  There  is  also  considerable 
thickening  of  the  serous  membrane. 


OBSERVATIONS  UPON  APPENDICITIS  381 

should  be  generally  accepted,  it  would  be  a  point  for  considera- 
tion whether  the  rheumatic  form  showed  any  characters  that 
served  to  differentiate  it  wholly  or  partially  from  the  other 
forms. 

In  order  to  prove  the  existence  of  "  a  rheumatic  appen- 
dicitis" much  investigation  over  a  long  period  of  time  will  be 
necessary.  The  position  to  be  aimed  at  is  clear  enough.  We 
need  to  show  on  clinical  evidence  a  connection  between  the 
two  diseases  and  to  demonstrate  a  common  cause.  In  addition 
to  this  we  require  to  be  able  to  produce  the  disease  in  animals 
with  the  infective  agent,  and  to  show  that  the  morbid  changes 
in  the  human  and  animal  tissues  are  of  a  like  nature. 

At  the  present  moment  the  definite  statement  may  be  made 
that  if  there  is  a  rheumatic  appendicitis  it  is  not  a  lesion 
which  is  often  met  with  in  the  general  acute  disease  in  child- 
hood. We  have  no  doubt  as  to  the  association  of  arthritis  and 
morbus  cordis  in  rheumatism  or  of  chorea  and  arthritis,  or 
again  of  chorea  and  morbus  cordis,  but  of  appendicitis  and 
these  lesions  experience  tells  a  very  different  tale.  If,  then, 
an  appendicitis  is  rheumatic  it  must  be  considered  one  of  the 
rarer  manifestations,  or  a  manifestation  the  occurrence  of 
which  points  to  an  unusual  incidence  on  the  part  of  the  infec- 
tion dependent  possibly  upon  some  individual  peculiarity. 
We  have  convinced  ourselves  in  the  last  ten  years  that  some 
explanation  of  this  nature  is  essential  if  a  rheumatic  form 
actually  exists.  So  strong  was  our  conviction  upon  this  point 
that  the  experimental  production  of  the  disease  came  to  us  as 
a  complete  surprise,  and  we  do  not  for  the  moment  lose  sight 
of  the  fact  that  great  caution  is  needed  in  applying  the  results 
of  experiment  to  human  pathology.  Nevertheless,  as  is  so 
often  the  case  in  research,  since  the  publication  of  our  results 
we  have  had  examples  of  the  occurrence  of  an  appendicitis 
apparently  of  rheumatic  origin  brought  to  our  notice,  and  we 
have  no  right  to  ignore  the  fact  that  for  many  years  various 
writers  have*  held  this  view  of  its  origin,  Kelynack,  Kretz, 
Beverley  Robinson  and  Alexander  Haig  among  others,  or  to 
forget  that  individual  experience  is  at  the  best  very  limited. 
An  unprejudiced  study  of  this  question  is,  we  feel,  deserving 
of  attention,  and  there  can  be  but  little  doubt  that  it  is  one 
which  can  eventually  be  settled.  This  is  the  more  to  be 
desired  because  the  abdominal  manifestations  of  rheumatism 


382  OBSERVATIONS  UPON  APPENDICITIS 

have  not  met  with  much  attention,  and  the  work  in  Germany 
and  our  own  results  upon  tonsillitis  give  a  new  impetus  to 
further  inquiry. 

The  form  of  appendicitis  which  would  first  attract  the 
attention  of  the  investigator  is  the  relapsing  one,  for  rheu- 
matism is  essentially  a  disease  of  that  nature,  and  it  is  rational 
to  postulate  that  such  a  process  as  we  see  every  day  occurring 
in  the  mitral  valve  might  also  occur  in  the  appendix. 

It  will  not  escape  the  reader  that  the  lesions  that  we  have 
illustrated  in  the  human  and  animal  appendices  are  strikingly 
similar,  the  plates  that  are  given  in  the  two  previous  papers  are 
most  convincing  upon  this  point.  We  see  the  diplococci  in  the 
tissues  and  their  destruction  in  the  walls  of  the  appendix.  The 
necrosis,  the  sero-fibrinous  exudation,  the  vascular  dilatation 
and  thrombosis,  the  leucocytic  infiltration  and  the  formation 
of  an  ulcer.  A  study  of  relapsing  appendicitis  in  man  has 
enabled  us  to  show  the  perivascular  fibrosis  and  replacement 
of  essential  tissues  by  scar  formation,  a  change  common  to 
many  infections  but  most  conspicuous  in  rheumatism  on 
account  of  the  rarity  of  suppuration  and  the  great  resistance 
to  the  disease.  Further,  a  study  of  the  human  appendix 
shows  us  with  increased  certainty  that  the  disease  is  more 
usually  the  result  of  a  blood  infection  than  of  a  local  invasion 
of  tissues  from  some  primary  cause  within  the  lumen. 

It  is  only  reasonable  to  suppose  that  secondary  factors  may 
arise  within  the  lumen  when  once  the  organ  has  been  diseased, 
which  lead  to  further  injuries.  The  inflamed  mucous 
membrane  produces  an  exudation  which,  becomes  mixed 
with  the  contents  of  the  bowel  and  when  inspissated  develops 
into  a  concretion  which,  just  as  a  gall-stone  in  the  gall- 
bladder, may  then  in  turn  produce  injury  and  inflamma- 
tion. The  appendix  itself  may  become  extraordinarily 
thickened  and  rigid  from  repeated  subacute  attacks  of  infec- 
tion, and  such  a  structure  must  be  liable  to  injury  from  blows 
or  sudden  strains,  particularly  as  the  disease  is  exceedingly 
frequent  at  the  athletic  age.  Again,  if  the  inflammation  is 
severe  but  localised  a  contraction  of  the  lumen  of  the  tube  at 
that  spot  is  to  be  expected,  and  behind  this  stricture  pent  up 
contents  are  very  likely  to  become  harmful.  The  muscular 
tissue  which  must  surely  serve  some  purpose  in  emptying 
the  contents  in   health  are  often  severely  damaged  as  our 


;._•_- 


(.■ 


'       - 


.- 


:0 


Recurrent  appendicitis  (human).     Section  of  the  submucosa  and  inner  muscular  coat  under  higher  magnifica- 
tion, illustrating  perivascular  fibrosis  with  infiltration  of  the  muscular  coat  by  the  fibrous  elements,  the  result 
of  previous  inflammation,  together  with  leucoeytic  infiltration  the  result  of  the  recent  attack. 


-.  7"   /--.  . 


&*»?./** 


*-  '"'.  ■    . ' '  •" y .is? ' '  ' 


i---   .  ■■'■ 


; -.-.  -~ 


...  •  .-..c',):i-: 


FIG.  105 
Recurrent   appendicitis  (human).      Section  of  the  outer  muscular  coat  and  serous   membrane 
under   the  same  magnification  as  the  preceding-,   showing-  perivascular  fibrosis,  the   result  of 
previous  inflammation,  together  with  leucoeytic  infiltration  the  result  of  the  recent  attack. 


OBSERVATIONS  UPON  APPENDICITIS  383 

illustrations  clearly  show,  and  this  damage  will  result  in  a 
tendency  to  the  stasis  of  the  contents  within  the  lumen. 

It  is,  then,  evident  that  the  problem  of  appendicitis  is  not  a 
simple  one.  We  do  not  suppose  that  even  if  the  cause  of 
any  particular  case  be  rheumatism  that  the  final  develop- 
ments will  be  necessarily  uncomplicated  by  the  secondary 
factors  described  above,  and  the  introduction  of  septic  infection 
as  a  complication  is  one  obvious  probability.  We  would  draw 
attention  to  the  remarkable  and  undoubted  fact  that  the 
intravenous  injection  of  the  diplococcus  in  the  rabbit  will 
produce  a  solitary  ulcer  in  the  appendix.  It  is,  perhaps,  one 
of  the  most  remarkable  experimental  results  we  have  ever 
seen,  and  it  throws  a  very  interesting  light  upon  the  pathology 
of  intestinal  ulceration  in  general,  opening  our  minds  to 
receive  new  facts  upon  the  occurrence  of  gastric  and  duodenal 
ulceration  in  man. 

The  amount  of  progress  that  we  have  made  upon  the  subject 
of  appendicitis  is,  we  admit,  only  small,  but  we  believe,  setting 
aside  all  question  of  the  rheumatic  origin,  we  have  put  forward 
and  illustrated  a  view  of  the  pathology  of  this  important 
disease,  or  more  correctly  sjmrptom  of  disease,  which  the 
future  will  show,  explains  its  nature  more  clearly  and  more 
correctly  than  any  hitherto  favoured  in  this  country.  In  brief 
our  view  is,  that  probably  the  great  majority  of  cases  of 
appendicitis  are  primarily  the  results  of  some  infection — and 
particularly  a  streptococcal  one — gaining  access  to  the  organ 
by  the  blood  stream. 


PART  III 

A    STUDY    OF   ACUTE    RHEUMATISM    BASED    UPON 
THE   RESULTS   OF  THE   PREVIOUS  RESEARCHES 

i.    THE  ETIOLOGY  AND  PATHOLOGY 

2.  SYMPTOMATOLOGY 

3.  DIAGNOSIS  AND  PROGNOSIS 

4.  TREATMENT 

5.  PREVENTION 


385  25 


THE  ETIOLOGY  AND   PATHOLOGY 

We  shall  attempt  in  this  article  to  consider  the  disease  termed 
"  acute  rheumatism  "  by  the  light  of  the  preceding  investiga- 
tions, indicating  their  bearing  upon  the  aetiology  and  pathology, 
symptoms,  diagnosis,  prognosis  and  treatment.  In  writing 
this  paper  we  realise  the  inadequacy  of  the  terms  "  acute 
rheumatism"  and  "rheumatic  fever,"  but  present  usage  has 
prevented  us  from  abandoning  them  and  employing  as  we 
should  prefer  the  general  term  rheumatism. 

(a)  The  ^Etiology 

The  first  step  is  a  consideration  of  the  older  explanations  of 
the  causation  and  the  part  that  they  take  in  the  evolution  of 
the  present  position  of  the  question.  It  is  not  to  be  supposed 
that  the  suggestions  put  forward  by  earlier  writers,  crippled 
though  they  were  by  limitations  in  methods  of  inquiry,  can 
be  thrown  aside  as  useless,  for  they  were  based  upon  observa- 
tions made  by  physicians  of  high  intelligence  and  deep  clinical 
insight. 

Cullen  attributed  the  disease  to  the  direct  influence  of  cold 
upon  the  joints  which  he  believed  to  be  vulnerable  on  account 
of  their  comparatively  thin  covering.  Here  he  thought  the 
inflammation  commenced,  and  from  them  to  generalise,  and 
we  have  in  this  theory  a  recognition  of  the  important  factor  of 
chill  in  the  causation  of  the  disease. 

J.  K.  Mitchell  suggested  that  the  primary  lesions  would  be 
localised  in  the  spinal  cord.  Chill  and  exposure  irritated  the 
sensory  nerve  fibres  over  a  wide  area  and  set  up  this  central 
disturbance  which  was  in  turn  reflected  to  the  nerves  of  the 
various  organs  and  tissues  and  thus  produced  the  manifesta- 
tions. This  view,  based  at  first  upon  a  study  of  cases  of 
arthritis  occurring  in  spinal  diseases,  was  elaborated  at  a  time 

387 


388  ETIOLOGY  AND  PATHOLOGY 

when  the  study  of  the  nervous  system  was  developing  with 
great  rapidity.  It  is  easy  to  recognise  in  writings  of  that  date 
(1831)  that  this  system  was  taking  too  exclusive  a  position  in 
the  explanation  of  clinical  facts,  but  the  theory  itself  has 
greatly  assisted  in  keeping  before  us  the  importance  of  the 
nervous  system  in  rheumatic  affections. 

The  chemical  theories  to  which  great  impetus  had  been  given 
by  the  classical  investigations  of  the  late  Sir  Alfred  Garrod 
looked  to  uric  acid  or  lactic  acid  as  the  exciting  cause.  In 
some  respects  the  writings  from  this  standpoint  have  seemed 
to  us  to  have  missed  their  mark  because  they  tended  to  throw 
overmuch  stress  upon  the  constitutional  peculiarities  of  the 
patient  and  to  minimise  the  external  factors  that  take  so 
important  a  part  in  the  causation  of  the  disease.  The  lactic 
acid  theory  originated  by  Prout  was  supported  by  Fuller  and 
Senator,  and  met  with  experimental  support  from  the  investiga- 
tions of  Sir  W.  B.  Richardson,  Rauch,  and  Sir  Walter  Foster. 
We  cannot  overlook  the  fact  that  Richardson  and  Rauch 
produced  definite  endocardial  and  pericardial  lesions  with 
lactic  acid  although  other  observers  failed  to  confirm  their 
results.  Nevertheless,  there  has  not  been  any  conclusive 
demonstration  of  an  excess  of  this  acid  in  the  tissues  and 
excretions  of  acute  rheumatism  during  the  course  of  the 
disease. 

Again  Dr.  P.  W.  Latham's  and  Dr.  Haig's  views  that  great 
importance  should  be  attached  to  uric  acid  in  the  production 
of  acute  rheumatism,  whether  acting  in  conjunction  with 
lactic  acid  or  by  itself,  have  not  met  with  any  convincing 
support  from  later  investigators. 

Theory  of  infection.  Over  a  century  ago  Saunders  suggested 
that  rheumatism  might  be  akin  to  malaria,  and  this  was 
supported  later  by  Maclagan,  but  modern  investigations  have 
shown  conclusively  that  the  two  diseases  are  wide  apart  from 
one  another. 

The  present  position  of  the  bacteriology  is  explained  in  the 
preceding  papers,  and  here,  without  further  discussion,  the 
disease  will  be  looked  upon  as  the  result  of  infection  by  a 
diplococcus  belonging  to  the  streptococcal  group. 

The  diplococcus  we  believe  to  be  present  in  all  probability 
in  the  tonsils  in  the  healthy  subject,  and  it  may  possibly  be 
present  in  many  other  situations.     Under  certain  circumstances 


ETIOLOGY  AND  PATHOLOGY  389 

and  particularly  in  individuals  whose  parents  have  suffered 
from  acute  rheumatism  this  diplococcus  develops  pathological 
properties,  gains  access  to  the  system,  and  sets  up  many  and 
various  manifestations.  We  do  not  suppose  that  the  causa- 
tion of  acute  rheumatism  is  to  be  summed  up  in  the  view  that 
it  is  due  entirely  to  the  invasion  of  the  diplococcus.  Its 
presence  in  the  tissues  is  no  doubt  essential,  but  there  are 
important  predisposing  factors  of  much  practical  interest,  and 
among  these  are  the  following. 

1.  Heredity.  This  is  a  striking  feature  which  we  interpret 
in  this  way.  The  rheumatic  infection  produces  poisons  of 
extreme  subtlety,  as  is  exemplified  by  the  remarkable  effect  it 
may  produce  upon  the  nervous  system  of  the  young,  altering, 
sometimes  for  years,  the  character  and  mental  stability. 
Further,  it  is  a  disease  which  does  not  protect  the  patient  from 
repeated  attacks  but  on  the  contrary  renders  him  more 
vulnerable.  As  a  result  a  constitutional  tendency — a  tissue 
proclivity  is  developed  which  we  believe  to  be  transmitted  in 
a  greater  or  lesser  degree  to  the  children. 

If  we  take  the  evidence  obtained  by  the  late  Dr.  W.  B. 
Cheadle  from  his  private  case-books  we  find  these  figures. 
In  thirty  consecutive  cases  twenty-three  gave  a  family  history, 
and  if  we  add  to  these  the  cases  with  chorea  and  erythema 
thirty-one  out  of  thirty-three  were  found  hereditary  ;  com- 
bining arthritis,  chorea  and  morbus  cordis,  103  out  of  180  gave 
a  family  history. 

Hospital  records,  though  less  accurate  are  sufficiently  con- 
vincing and  carry  the  additional  weight  that  they  have  been 
compiled  by  various  independent  writers  who  have  each 
arrived  at  the  same  general  conclusion. 

Sometimes  it  happens  that  a  mother  in  late  pregnancy  is 
the  victim  of  an  attack  of  acute  rheumatism,  and  then  we  find 
that  a  different  event  may  result.  The  infant  may  be  born, 
not  with  a  tendency  to  the  disease,  but  with  the  active  disease 
actually  present.  Morbus  cordis  may  develop  in  utero,  and 
in  one  case  we  demonstrated  the  diplococcus  in  vegetations  on 
the  mitral  valve  the  second  day  after  birth.  Accordingly  we 
hold  that  in  exceptional  cases  there  may  be  direct  transmission 
of  the  diplococcic  infection  through  the  placental  circulation. 

2.  Sex  incidence.  In  childhood  rheumatism  occurs  more 
frequently  in  females  than  in  males,  thus  in  500  cases  we  found 


390  .ETIOLOGY  AND  PATHOLOGY 

319  females  and  181  males.  A  very  interesting  point  arises  in 
connection  with  this  sex  incidence.  The  nervous  system  is 
much  more  frequently  attacked  in  the  female  child,  and  chorea 
largely  accounts  for  the  predominance  in  the  numbers.  With 
chorea  is  associated  mitral  stenosis,  and  we  find  that  this 
lesion  which  does  not  disappear  as  does  the  chorea  in  adult 
life  is  far  more  frequent  in  the  female.  To  us  it  has  appeared 
probable  that  some  intrinsic  peculiarities  of  the  female  meta- 
bolism may  account  for  what  we  believe  to  be  a  broad  general 
rule,  viz.  that  rheumatism  in  this  sex  tends  to  be  less  acute 
but  more  obstinate.  Doubtless  it  is  a  rule  with  many  excep- 
tions, but  our  experience  has  also  led  us  to  think  that  in  the 
child,  at  least,  rheumatism  is  more  acutely  fatal  in  the  male, 
although  as  a  result  of  chronic  heart  disease  and  the  greater 
number  of  females  attacked,  the  actual  mortality  among  them 
is  the  higher.  Thirty-six  acutely  fatal  cases  under  our 
observation  were  made  up  of  twenty-two  males  and  fourteen 
females. 

When  adult  life  is  reached  it  is  clear  that  the  male  is  more 
exposed  to  danger  by  nature  of  his  employment,  and  in  this 
sex  the  death  rate,  partly  from  the  acute  disease  and  partly 
from  its  previous  injuries,  rises  in  frequency. 

3.  Age  incidence.  The  age  incidence  fully  bears  out  the  view 
that  rheumatism  is  an  infective  disease.  Almost  any  age  is 
liable  to  an  attack,  and  we  meet  with  cases  at  two  years  or 
even  younger,  but  it  is  not  until  after  five  years  that  the 
numbers  begin  to  increase  rapidly,  and  throughout  childhood 
rheumatism  is  very  frequent  in  this  country.  After  puberty 
there  is  a  decided  fall  in  the  frequency  of  nervous  manifesta- 
tions of  the  disease,  and  though  it  is  common  enough  through 
adolescence  and  early  adult  life,  the  liability  is  less  than  in 
childhood  and  the  manifestations  less  varied. 

There  are  several  interesting  considerations  that  arise  out  of 
the  question  of  age  and  its  relation  to  rheumatism.  Among 
these  may  be  mentioned  the  possible  influence  of  acquired 
habits  in  modifying  the  results  of  the  rheumatic  infection. 
Thus,  for  example,  if  we  suppose  an  adult  the  victim  of  acute 
rheumatism  in  childhood  to  live  a  life  such  as  we  associate 
with  the  development  of  "  goutiness,"  and  then  to  be  attacked 
by  the  rheumatic  infection,  it  is  an  interesting  speculation  as 
to  whether  then  he  would  not  develop  acute  gout.     This  seems 


ETIOLOGY  AND  PATHOLOGY  391 

to  us  a  very  possible  occurrence,  for  it  is  quite  conceivable 
that  the  inflammatory  reaction  to  the  infection  might  be 
intensely  painful  and  that  in  the  damaged  tissues  and  exuda- 
tions biurate  of  soda  might  be  formed  in  the  process  of  cell- 
necrosis. 

Again,  in  the  old  or  prematurely  aged  the  rheumatic  infection 
might  well  be  associated  with  chronic  changes  of  a  stubborn 
character  and  degenerative  lesions  in  the  affected  tissues,  such 
as  ulceration  of  cartilage  and  bone.  We  may  seem  to  be 
drifting  here  into  pure  speculation  but  there  can  be  no  doubt 
that  a  disease  of  the  inveterate  character  of  rheumatism  offers 
a  valuable  field  for  the  study  of  the  influence  of  changes  in  the 
human  tissues  resulting  from  age  or  acquired  habits  upon  the 
behaviour  of  an  infective  process. 

These  preceding  considerations  which  are  concerned  with 
the  individual  attacked  by  rheumatism  raise  the  question  as 
to  whether  there  is  a  type  that  can  be  recognised  as  predisposed 
to  the  disease.  This  is  the  more  interesting  at  the  present 
time  because  the  numerous  modern  instruments  and  methods 
of  precision  coupled  with  the  increasing  "specialism"  of 
medicine  tends  to  lead  us  into  the  danger  of  not  realising  the 
general  and  more  indefinable  effects  of  disease,  and  we  are 
possibly  inclined  to  believe  that  our  accurate  knowledge  of 
disease  in  man  is  greater  than  it  is  in  reality. 

There  has  been  handed  down  to  us  that  in  the  adult  the 
rheumatic  subject  has  a  coarse  greasy  skin  and  muddy  com- 
plexion, but  in  the  child  this  is  certainly  not  the  case.  Such 
children  are  often  fair-haired,  with  a  bright  alert  manner,  clear 
skin,  but  somewhat  fragile  appearance.  They  are  excitable 
and  easily  tired,  imaginative  and  subject  to  night  terrors. 
More  than  others  they  appear  to  suffer  from  sore-throats  and 
unhealthy  tonsils.  Digestive  disturbances  are  frequent  and 
take  the  form  of  attacks  in  which  there  may  be  vomiting  with 
pale  stools,  or  again,  mucous  colitis.  It  is  difficult  to  decide 
how  much  in  the  constitutional  weakness  is  the  result  of  some 
actual  invasion  by  the  infection  in  a  mild  degree,  but  all  who 
are  well  acquainted  with  these  children  realise  that  they 
frequently  present  similar  characteristics. 

One  of  the  advances  in  our  conception  of  rheumatism 
furnished  by  the  view  that  it  is  an  infection  is  the  realisation 
that   in    addition   to    the   peculiarities    dependent    upon   the 


392  .ETIOLOGY  AND  PATHOLOGY 

individual  we  have  also  to  remember  that  the  infection  itself 
possesses  certain  characteristics.  These  are  difficult  enough  at 
present  to  express  in  clear  terms,  but  they  are  widely  recognised. 
A  consideration  of  these  brings  us  to  the  study  of  the  influence 
of  climate  and  season,  locality,  surroundings,  atmospheric 
conditions,  and  other  infections. 

Climatic  influences.  Although  rheumatism  would  appear  to 
be  ubiquitous,  there  is  agreement  that  temperate  climates  in 
which  there  are  considerable  alterations  in  humidity  favour 
the  infection.  In  this  country  the  disease  is  very  frequent, 
and  it  appears  to  us  that  the  lack  of  sun,  cold  winds  and  damp, 
must  greatly  favour  inflammations  of  the  throat.  We  have 
repeatedly  noticed  that  when  after  a  spell  of  dry  heat  with 
dust,  cold  rain  and  winds  have  followed,  an  outbreak  of  rheu- 
matism occurs.  The  dust  has  favoured  irritable  affections  of 
the  throat  and  the  cold  and  damp  have  precipitated  the 
occurrence  of  chills  and  tonsillitis. 

Seasonal  influences.  Intimately  associated  with  the  fore- 
going is  the  liability  for  rheumatism  to  increase  when  the  late 
autumn  and  early  spring  seasons  come  round. 

Epidemic  influences.  There  would  seem  little  doubt,  for 
there  are  a  considerable  number  of  independent  observations 
upon  this  point,  that  the  frequency  of  the  disease  may  increase 
so  much  in  some  years  as  to  justify  the  term  of  epidemic  being 
applied  to  the  outbreak.  This,  however,  would  not  seem  to 
be  a  general  but  more  or  less  local  occurrence  as  is  the  case 
with  polio-myelitis.  We  recall  in  recent  years  a  remarkable 
frequency  of  the  disease  in  North  London,  and  letters  from 
medical  men  apprised  us  of  the  same  occurrence  in  country 
districts. 

Such  events  as  these  will  naturally  raise  in  our  minds  the 
possibility  that  rheumatism  may  not  only  be  infective  but 
infectious.  There  is  no  doubt  that  several  children  may  be 
attacked  at  the  same  time  in  one  household,  and  we  have  met 
with  instances  of  two  children  sleeping  in  the  same  bed  de- 
veloping the  disease.  Nevertheless,  it  would  be  wrong  to 
promulgate  the  view  that  this  is  a  frequent  event  or  one  that 
does  not  admit  of  other  explanations.  Tonsillitis  is  certainly 
apt  to  spread  among  the  predisposed,  and  to  this  extent  it  is 
possible  that  members  of  a  rheumatic  family  may  be  a  danger 
to  one  another.     Yet,   on  the  other  hand,   to  one  of  these 


.ETIOLOGY  AND  PATHOLOGY  393 

examples  there  are  literally  hundreds  in  which  no  such  associa- 
tion can  be  recognised,  and  it  must  be  admitted  that  in  the 
exceptions  there  may  be  some  other  influence  at  work  such  as 
an  unhealthy  house  or  lack  of  care  on  the  part  of  the  parents 
for  children  who  are  predisposed  by  inheritance  and  in  them- 
selves delicate. 

Influence  of  malsanitation.  There  is  evidence  that  insanitary 
houses  may  be  a  cause  of  acute  rheumatism  which  may  assume 
a  "septic"  or  "  typhoidal  "  character.  In  such  cases  one 
individual  may  develop  a  "septic"  pneumonia,  another 
scarlet  fever,  a  third  acute  rheumatism.  There  is  no  reason  to 
look  upon  this  occurrence  as  an  evidence  that  rheumatism  is 
an  attenuated  pyaemia,  for  the  "  septic  "  type  may  just  as  well 
be  explained  by  the  supposition  that  the  malsanitation  has 
either  increased  the  special  virulence  of  the  diplococcus  or 
lowered  the  resistance  of  the  individual,  or  caused  both  these 
changes.  We  would  particularly  emphasise  that  we  do  not 
suppose  that  the  diplococcus  possesses  some  remarkable 
constant  feature  which  results  in  its  producing  invariably  the 
same  results  in  the  human  body.  We  regard  it  as  capable  of 
altering  considerably  in  virulence  under  different  circum- 
stances. 

Influence  of  other  infections.  Diseases  such  as  scarlet  fever 
and  measles,  and  we  may  add  diphtheria,  by  causing  sore  throat 
favour,  we  believe,  the  danger  of  rheumatism,  especially  in  the 
predisposed. 

The  influence  of  locality  upon  acute  rheumatism  is  an  exceed- 
ingly difficult  study  to  which  we  believe  fresh  investigation 
might  be  directed  in  this  country  with  useful  results.  Sir 
Arthur  Newsholme  many  years  ago  pointed  out  that  it  was  an 
urban  disease  associated  with  a  low  level  of  surface  water.  It 
is  possible  that  the  medical  profession  hardly  yet  recognises 
how  frequent  this  disease  is  among  the  children  in  London. 
In  our  Children's  Hospitals  it  is  met  with  in  all  the  medical 
wards  and  in  numbers  in  the  out-patient  departments. 

We  have  seen  too  many  examples  of  cases  arising  in  families 
who  have  changed  residences  and  had  the  misfortune  to  drift 
into  a  damp  house  not  to  feel  convinced  that  cold  damp  is  most 
injurious,  and  one  of  the  results  that  we  have  repeatedly 
noticed  under  these  circumstances  has  been  the  persistent 
character  of  the  rheumatic  lesions.     We  believe  that  a  rheu- 


394  ETIOLOGY  AND  PATHOLOGY 

matic  child  living  in  a  patently  damp  house  and  low-lying 
neighbourhood  is  very  likely  to  develop  a  form  of  arthritis 
which  is  indistinguishable  from  so-called  rheumatoid  arthritis. 
It  also  appears  to  us  that  there  is  need  for  some  further  inquiry 
into  the  influence  of  residence  upon  rheumatism,  for  we  have 
been  struck  with  the  fact  that  not  uncommonly  a  child  admitted 
into  hospital  makes  a  steady  and  good  recovery,  and  yet 
repeatedly  breaks  down  again  on  returning  home,  as  if  this 
return  brought  him  into  some  peculiar  surroundings  which 
either  roused  up  latent  processes  in  his  tissues  or  reinfected 
him.  A  clay  soil  is  looked  upon  as  the  most  unfavourable  one 
for  the  rheumatic  but  it  is  clear  that  the  drainage  of  any  soil 
must  also  be  taken  into  account.  With  houses,  too,  the 
question  of  damp  cellars,  thin  walls,  ill-fitting  casements,  and 
other  weaknesses  that  result  from  cheap  and  bad  work  clearly 
require  consideration. 

Adults  are  less  liable  to  develop  rheumatism  but  the  same 
general  facts  hold  good  as  to  damp,  exposure,  chills  when 
heated,  and  malsanitation.  Many,  we  must  remember,  under 
these  circumstances  do  not  develop  the  disease,  but  are  already 
the  victims  of  it  from  childhood. 

Among  surroundings  not  yet  considered  we  must  mention 
the  elementary  schools.  It  is  very  possible  that  where  there 
are  numerous  colds  and  sore  throats  among  the  scholars  the 
rheumatic  child  may  suffer  as  a  consequence.  This  is  a 
difficulty  which  cannot  be  avoided  where  large  numbers  of 
children  are  collected  together,  but  that  it  can  be  lessened  by 
simple  precautions  is  undoubted. 

Dietetic  influences.  We  have  entirely  abandoned  the  idea 
that  diet  has  any  influence  in  the  incidence  of  acute  rheu- 
matism in  childhood,  for  we  can  find  no  practical  support  for 
its  truth  and  hold  that  it  has  been  one  of  the  mistaken  results 
not  uncommon  in  medical  history  of  over-generalisation  from 
some  important  clinical  observation.  The  chemical  theories 
centring  round  the  discovery  of  uric  acid  and  its  antecedents 
are,  we  believe,  the  basis  for  this  idea  of  the  influence  of  diet. 
We  look  forward  to  the  time  when  the  theory  that  too  much 
meat  is  responsible  in  any  way  for  this  disease  in  the  young 
will  disappear,  however  much  imprudence  in  diet  may  modify 
its  course  in  later  life. 

In  general  it  may  be  confidently  stated  that  those  surroundings 


ETIOLOGY  AND  PATHOLOGY  395 

which  are  associated  with  poverty  and  neglect  are  responsible 
for  much  of  the  acute  rheumatism  so  rife  in  this  country. 

(b)  The  Pathology 
i.  The  Diplococcus  Rheumaticus 

A  brief  account  of  the  chief  characteristics  of  the  diplococcus 
will  be  given  here  in  a  summary. 

It  is  a  small  micrococcus  0.5  /a  in  diameter  and  grows 
usually  in  pairs  or  in  short  chains.  As  a  rule  it  does  not  show 
a  capsule,  but  in  the  human  tissues  an  appearance  of  capsulation 
may  be  occasionally  noticed. 

It  stains  readily  with  aniline  dyes,  but  does  not  retain 
Gram's  stain  with  great  tenacity. 

Degenerative  forms  are  common,  and  the  micrococcus  then 
may  become  swollen  or  pear-shaped,  and  lose  its  staining 
properties. 

Cultural  characteristics.  In  Bouillon  at  37 °  C.  there  is 
turbidity  with  a  slight  flocculent  deposit  in  twenty-four  hours. 
In  three  days  the  fluid  becomes  clear  and  there  is  a  distinct 
deposit.     The  medium  becomes  acid. 

On  blood-agar — one  of  the  most  favourable  media.  In 
twenty-four  hours,  minute  white  colonies  are  visible  :  these 
tend  to  remain  discrete  and  to  alter  the  blood  pigment  to  a 
rusty-brown  colour.  Upon  this  medium  the  micrococcus  will 
live  for  long  periods  of  time. 

Milk  and  bouillon.  Slightly  acidified  with  lactic  acid. 
This  is  a  useful  medium  for  isolation  of  the  micrococcus. 
In  twenty-four  hours  the  milk  is  coagulated. 

Vernon-Shaw  used  a  medium  of  glycerine  veal  broth  con- 
taining 2  per  cent,  peptone  and  1  per  cent,  alkaline  to  phenol- 
phthalein.  Beattie  directed  attention  to  a  very  definite 
reaction  in  the  production  of  acid  and  precipitation  of  the  bile 
salts  in  McConkey's  bile  salt  lactose  broth. 

Gelatine  (stab).  In  forty-eight  hours  minute  colonies  appear 
along  the  track  of  the  needle  :   there  is  no  liquefaction. 

The  micrococcus  possesses  a  considerable  power  of  producing 
acid,  and  Triboulet  and  Coyon,  Walker  and  Ryffel,  Shaw  and 
Berger  investigated  these  acids  and  have  shown  that  they  vary 
with  the  medium  in  which  the  micro-organism  is  grown. 
Walker  and  Ryffel  have  particularly  directed  attention  to  the 


396  ETIOLOGY  AND  PATHOLOGY 

large  quantity  of  formic  acid  that  the  micro-organism  forms 
and  have  extracted  this  acid  from  the  bodies  of  the  micrococci 
themselves.  This  micrococcus  retains  its  vitality  in  the  dry 
state  for  many  months. 

ii.  The  Morbid  Anatomy 

The  experimental  study  of  rheumatism  coupled  with  the 
minute  investigation  of  the  tissues  in  man  gives  a  most  con- 
vincing proof  of  the  nature  of  the  disease.  There  are,  in  fact, 
few  diseases  the  symptoms  of  which  can  be  more  satisfactorily 
explained  if  it  be  remembered  that  the  exact  nature  of  the 
poisons  which  are  elaborated  are  as  yet  unknown. 

The  disease  is  the  result  of  numerous  separate  lesions  ;  it  is 
also  one  to  which  the  human  frame  offers  great  resistance  ; 
lastly,  it  varies  as  do  other  diseases  in  virulence.  We  see  in 
the  rheumatic  process  what  we  see  in  other  infections,  the 
tendency  to  widespread  dissemination  in  the  tissues  of  the 
young,  and  an  increasing  localisation  in  those  of  the  adult. 
We  find,  too,  the  older  tissues  when  they  are  attacked  throwing 
off  the  effects  of  the  disease  with  more  difficulty. 

In  the  subcutaneous  nodule  we  discover  the  clue  to  the 
structure  of  the  rheumatic  lesions.  In  this  there  is  a  deposit 
of  the  infective  agent  and  evidence  of  its  results  in  the  swollen 
connective  tissue  at  the  periphery,  and  the  exudation  and 
tissue  necrosis  in  the  centre.  We  also  find  the  proof  of  tissue 
reaction  in  distended  blood  capillaries  and  leucocytic  infiltra- 
tion. Should  the  nodule  be  unusually  large  and  chronic  we 
recognise  also  the  usual  results  of  an  imperfect  victory  in  the 
presence  of  scar  tissue. 

Aschoff,  Tawara  and  Carey  Coombs  have  taken  us  a  step 
further  by  the  study  of  the  still  more  minute  submiliary  nodules 
in  which  they  find  certain  large  multinucleated  cells  which 
they  consider  to  be  peculiar  to  the  disease.  Since  the  investiga- 
tions of  these  writers  we  have  studied  these  cells  and  have 
verified  the  truth  of  their  descriptions,  with  the  greater 
interest  it  may  be  added,  because  without  appreciating  their 
specific  structure  we  had  already  depicted  the  submiliary 
nodule.  To  quote  from  Carey  Coombs,  "  the  submiliary 
nodules  in  myocardial  rheumatism  consist  of  rounded  or 
fusiform  areas  formed  by  large  spindle-shaped  cells  lying  in 
the    intermuscular    trabecular    of    connective    tissue."     The 


$&, 


<Dt  .  *,,<^»,*>  "  • 


FIG.   106 

Section  of  ;i  sub-miliary  nodule.  We  are  indebted  for  this  illustra- 
tion to  Mr.  H.  G.  Bntterfield.  Following  his  description,  A  indicates 
the  main  giant-cell  lesion  ;  IS,  smaller  cells  with  single  nuclei  having 
precisely  the  same  staining'  reactions  as  the  giant-cell.  This  cell  is 
in  obvious  association  with  the  blood-vessel,  the  endothelial  cells  of 
which  differ  from  it  onlyin  possessing  single  nuclei.  Mr.  Bntterfield 
believes  that  the  giant-cell  i~  built  np  by  the  fusion  of  several  endo- 
thelial cells  of  the  same  nature  as  those  in  the  capillary  wall,  for 
under  magnification,  1000,  some  of  its  components  appear  to  possess 
a  definite  cell  outline.  This  lesion  was  found  in  the  epicardinm  of 
the  left  ventricle  of  a  case  of  acute  rheumatic  carditis  in  which 
organisms  corresponding  to  the  diplococcus  of  Poynton  and  Paine 
were  found  everywhere  in  the  heart.  Vide  ''Heart,"  vol.  iii.  Xo.  2. 
Feb.  1912. 


ETIOLOGY  AND  PATHOLOGY  397 

average  size  of  them  he  would  estimate  as  in  length  somewhat 
less  than  400  ju-  The  special  cells  following  the  same  writer 
are  much  larger  than  the  fibroblasts  of  ordinary  inflammatory 
reactions  ;  to  which  in  other  respects  they  most  closely 
approximate.  They  are  often  multinucleated,  the  chromatin 
substance  of  the  nuclei  in  most  cases  appearing  as  a  sharply 
defined  margin  with  a  small  central  mass  or  masses  ;  the  rest 
of  the  nucleus  takes  no  stain  and  thus  gives  to  the  cell  a 
vacuolated  appearance.  They  are  surrounded  by  plasma  cells 
and  leucocytes  chiefly  of  the  mononuclear  variety.  The 
nodules  frequently  arise  in  connection  with  an  arteriole  either 
around  it  or  even  in .  the  wall  itself,  and  their  eventual  fate 
appears  to  be  cloudy  swelling  or  cicatrisation. 

Coombs,  Miller  and  Kettle  have  recently  advanced  this 
subject  a  step  further  by  demonstrating  the  submiliary  nodules 
in  the  experimental  lesions  produced  by  the  diplococcus  ;  results 
which  they  published  in  the  Lancet  of  November  2,  1912. 

One  warning  we  would,  however,  venture  to  give  and  that 
is  against  relying  upon  their  presence  as  a  criterion  of  acute 
rheumatism  ;  and  their  absence  as  a  criterion  of  the  non- 
rheumatic  nature  of  a  lesion.  This  procedure  would  narrow 
the  horizon  of  acute  rheumatism  down  to  a  single  element  in 
morbid  histology,  and  so  far  as  our  attitude  is  concerned,  would 
destroy  the  broad  basis  of  clinical,  experimental,  pathological 
and  bacteriological  observation  upon  which  we  have  built  up 
our  view  of  the  disease.  Admitting  then  the  value  of  these 
observations  we  would  submit  that  these  cells  and  nodules 
may  only  represent  a  particular  phase  of  the  rheumatic  pro- 
cesses in  the  tissues  and  one  which  need"  not  always  be  forth- 
coming. 

When  once  the  intimate  structure  of  the  subcutaneous  and 
submiliary  nodules  have  been  mastered  the  elements  of  the 
morbid  anatomy  of  acute  rheumatism  are  understood.  The 
pericardial,  endocardial,  myocardial,  arthritic,  pleural  and 
meningeal  lesions  are  all  of  the  same  nature  when  due  allow- 
ances are  made  for  the  anatomy  of  the  various  structures  and 
their  particular  resistance  to  the  infection. 

The  Joints  and  Connective  Tissues.  In  general  terms  and 
considering  both  the  immature  and  mature  tissues,  the  joints 
are  the  most  vulnerable  structures  although  their  power  of 
recuperation  is  far  greater  than  that  of  a  cardiac  valve. 


398  ETIOLOGY  AND  PATHOLOGY 

Arthritis.  In  acute  rheumatic  arthritis  the  synovial  fluid  is 
bloodstained,  the  synovial  membrane  swollen  and  extremely 
hypersemic.  Minute  haemorrhages  occur  in  the  synovial  tissues, 
and  the  retiform  tissue  is  infiltrated  with  leucocytes.  In 
addition  the  connective  tissue  of  the  capsule  of  the  affected 
joint  is  frequently  swollen  and  infiltrated  with  serous  exudation. 

When  the  process  is  more  prolonged  the  arthritic  exudation 
becomes  sero-fibrinous,  and  a  plastic  deposit  may  line  the 
cavity. 

There  may  be  considerable  implication  of  the  surrounding 
tendons  in  the  severe  arthritis,  and  in  some  cases  in  childhood 
the  tendons  seem  to  suffer  more  than  the  joints  themselves. 
The  changes  in  these  structures  are  of  the  same  nature  as  those 
in  the  capsules  of  the  joints. 

As  a  rule  the  subsidence  of  the  inflammation  is  rapid,  and 
the  recovery  is  usually  complete. 

We  need  only  repeat  here  that  cultures  from  the  arthritis 
exudations  are  generally  sterile,  and  in  our  opinion  in  the 
present  state  of  our  knowledge  exploration  for  the  pur- 
pose is  seldom  a  wise  procedure,  for  the  micrococci  are 
mostly  destroyed  in  the  tissues  and  in  the  cells  of  the  arthritic 
exudation. 

We  come  now  to  a  problem  which  is  deserving  of  the  greatest 
attention.  It  is  repeatedly  stated  that  the  arthritis  of  acute 
rheumatism  subsides  rapidly  and  completely,  and  that  it  is 
very  unusual  for  any  local  injury  to  persist  after  the  attack. 
With  this  we  are  in  general  agreement  although  we  have  met 
with  very  definite  examples  of  one  joint,  among  many  which 
subsided,  remaining  painful  and  swollen  and  passing  into  a 
condition  of  "  rheumatoid  arthritis."  It  is  to  be  expected  that 
the  acute  form  of  rheumatic  arthritis  would  as  a  rule  subside, 
for  it  is  a  synovitis  and  the  affection  rapidly  destroyed,  but 
there  are  other  forms  of  rheumatic  arthritis,  we  believe,  both 
in  the  young  and  the  adult.  Cases  which  begin,  as  do  other 
rheumatic  lesions,  gradually,  and  with  warnings  which  are 
possibly  overlooked  and  which  run  a  tedious  and  sometimes 
crippling  course.  Every  variety  is  found.  Sometimes  in  a 
child  there  is  distension  of  the  cavity  of  a  joint  with  fluid  from 
which  the  diplococcus  may  be  isolated  and  from  which  there 
may  be  excellent  but  slow  recovery  ;  or  again,  at  an  early  age 
the  course  may  be  extremely  chronic.     In  young  adults  the 


ETIOLOGY  AND  PATHOLOGY  399 

process  may  be  not  only  prolonged  but  malignant  in  type,  and 
great  damage  result.  Associated  with  mitral  stenosis  there 
may  be  an  equally  slow  damage  to  the  joints,  and  in  the  adult 
a  chronic  arthritis  with  deformities  may  follow.  That  all  cases 
of  subacute  and  chronic  non-suppurative  arthritis  are  not 
rheumatic  is  undoubted,  but  to  maintain  that  the  rheumatic 
infection  does  not  produce  every  kind  of  arthritic  injury 
appears  to  us  to  be  mistaken.  The  great  difficulty  at  the 
present  time  is  to  demonstrate  the  cause  in  the  particular  case, 
but  we  hold  that  this  infection  may  damage  synovial  mem- 
brane, capsule,  cartilage  and  bone.  It  may  attack  small  as 
well  as  large  joints,  and  may  even  in  the  young  sometimes 
produce  a  very  chronic  spondylitis  deformans  ;  or  in  a  great 
toe  joint  an  acute  inflammation  almost  indistinguishable  from 
a  gouty  arthritis. 

A  study  of  the  connective  tissues  of  the  synovial  membranes 
both  in  man  and  in  experimental  arthritis  gives  a  very  clear 
idea  of  the  cardinal  processes  that  occur. 

When  acute  there  are  active  hyperemia  and  swelling  of 
tissue,  exudation,  leucocytosis  and  necrosis,  when  chronic, 
perivascular  fibrosis  occurs  with  the  usual  diminution  of  the 
calibre  of  the  small  blood-vessels  and  consequent  imperfect 
nutrition  of  the  synovial  structures.  The  tendon  sheaths  as 
well  as  the  tendons  themselves  often  suffer  and  an  exudation 
results  which  in  the  worst  cases  is  followed  by  painful  adhesions. 
Local  periostitis  around  the  affected  joints  is  met  with  both  in 
childhood  and  later  life,  and  in  the  young  is  often  associated 
with  the  development  of  subcutaneous  nodules.  Such  periostitis 
may  also  occur  at  a  distance  from  an  affected  joint. 

The  subcutaneous  nodules  having  already  been  described,  it 
remains  here  to  comment  upon  their  peculiar  distribution, 
along  tendon  sheaths  and  over  bony  prominences.  In  the 
paper  written  with  Dr.  Still  it  was  shown  that  the  same  process 
might  be  occurring  in  the  connective  tissue  without  producing 
visible  swelling,  and  it  would  seem  to  us  that  the  visibility  of 
the  nodule  is  largely  dependent  upon  the  fact  that  the  least 
swelling  is  thrown  into  relief  when  it  occurs  over  a  bony 
prominence,  and  thus  our  attention  is  arrested.  Yet  there  is 
probably  also  another  factor,  and  this  is  the  amount  of  move- 
ment, pressure  and  friction  to  which  the  tissues  over  these 
bony  prominences  are  exposed,  in  other  words  there  is  an 


400  ETIOLOGY  AND  PATHOLOGY 

element  of  injury  concerned  which  increases  the  severity  of  the 
local  infection  in  these  positions. 

The  distribution  along  tendon  sheaths,  though  probably 
influenced  by  the  movements  of  the  tendons,  is  also,  we  think, 
dependent  upon  the  synovial  sheath  being  in  nature  akin  to 
the  pericardium,  and  that  the  process  in  this  structure  is 
particularly  active.  These  nodules  along  the  tendon  sheaths 
which  occur  with  so  little  disturbance  are  most  interesting 
when  the  reader  studies  them  in  connection  with  the  pathology 
of  chorea.  Nodules  vary  very  much  in  duration  from  a  few 
days  to  many  months.  Usually  they  disappear  entirely,  but 
if  they  are  large  some  thickening  will  remain. 

Doubtless  the  fascice  suffer  much  in  rheumatism,  and  with 
the  fasciae  the  muscles  and  nerves  also.  The  term  fibrositis 
coined  by  Sir  William  Gowers  is  a  useful  one  in  this  relation, 
but  it  is  one  which  is  very  open  to  abuse.  Pathologists 
recognise  that  any  infection  travelling  in  the  blood  stream  gets 
a  foothold  in  the  tissues  by  escaping  from  the  minute  capillaries 
running  in  the  connective  tissues  binding  together  the  various 
organs.  If  fibrositis  is  used  then  to  denote  a  specific  disease  it 
can  only  result  in  confusion,  for  if  ever  there  was  a  condition 
that  was  truly  a  symptom,  it  is  this  one.  Rheumatic  fibrositis 
is  frequent  and  occurs  at  all  ages,  for  even  in  young  children 
we  meet  with  stiffness  of  the  muscles,  lumbago  and  intercostal 
pains.  In  adults  these  symptoms  are  far  more  frequent  and 
more  chronic.  The  actual  proof  of  the  cause  of  any  particular 
fibrositis  is  extremely  difficult  but  the  clinical  evidence  in 
favour  of  a  rheumatic  form  is  overwhelming.  In  severe  cases 
we  can  detect  deep-seated  tender  nodules  in  the  muscles 
arising  in  their  fasciae.  The  work  of  Froriep  long  ago  directed 
our  attention  to  these  changes,  and  Professor  Stockman  in  this 
country  has  done  much  to  impress  their  importance  upon  us  in 
recent  years. 

To  summarise  at  this  point  the  results  that  we  should  be 
prepared  to  meet  with  from  our  investigations  upon  the 
pathology  of  arthritis  and  fascial  lesions :  These  would  be 
localised  deposits  of  the  diplococcus,  swelling  and  infiltration 
of  connective  tissue,  necrosis  and  exudation,  capillary  haemor- 
rhages with  the  formation  of  nodules  varying  in  size  from  the 
submiliary  to  those  easily  palpable  to  the  fingers  when  lying 
deep,  or  as  large  as  a  filbert  when  subcutaneous.     Theoretically 


.ETIOLOGY  AND  PATHOLOGY  401 

no  fasciae  would  be  exempt  although  there  is  no  doubt  that 
some  regions  are  more  affected  than  others.  When  the 
muscles  grow  older  with  advancing  years  it  is  easily  realised 
how  these  changes  may  produce  great  pain  and  crippling,  for 
if  fibrosis  occurs  and  sensory  nerves  are  implicated  the  har- 
monious and  painless  contractions  of  the  muscular  fibres  will 
be  interfered  with,  and  in  the  early  stage  of  infiltration  and 
connective-tissue  swelling  the  same  must  occur  and  be  probably 
more  widespread  and  accompanied  by  a  distressing  sense  of 
muscular  weakness. 

A  very  interesting  subject  for  study  is  the  individual 
differences  in  reaction  to  the  rheumatic  infections  in  these 
tissues.  In  some  instances  we  find  a  remarkably  widespread 
pufnness  of  the  affected  regions,  giving  rise  in  the  hands  to 
much  swelling  and  difficulty  in  closing  the  fingers.  In  other 
cases  there  are  numerous  subcutaneous  nodules  which  give 
rise  to  little  or  no  pain  ;  in  others  the  periosteal  inflammation 
is  considerable  and  the  bones  around  the  joint  may  be  in  the 
adult  very  tender.  The  extent  to  which  these  differences  are 
dependent  upon  the  infection  or  upon  the  individual  is  a 
difficult  question  for  solution. 

Under  the  section  of  ^Etiology  we  have  expressed  our  con- 
viction that  acute  rheumatism  is  a  disease  that  is  not  dependent 
upon  dietetic  influences  ;  we  do  not,  however,  deny  that  in  the 
adult  and  elderly  persistent  errors  in  diet  will  produce  injurious 
effects  upon  all  tissues  and  thus  tend  to  modify  the  results 
of  the  rheumatic  infection.  Simple  wear  and  tear  of  the  tissues 
we  should  suppose  would  have  also  an  important  effect  in  the 
same  direction. 

Pathological  changes  in  the  heart  and  pericardium.  Simple 
pericarditis.  As  a  result  of  deposition  of  the  diplococci, 
hyperemia  and  capillary  haemorrhages  result  with  swelling  of 
the  connective  tissue  and  coagulation  necrosis  of  the  tissue 
cells,  exudation  of  serum  and  diapedesis  of  leucocytes  from 
the  blood  capillaries. 

The  endothelium  lining  the  pericardial  sac  is  destroyed  in 
many  areas  and  there  is  an  exudation  into  the  cavity  varying 
in  character  according  to  the  duration  and  virulence  of  the 
process.  Thus  it  may  be  bloodstained,  serous,  sero-fibrinous, 
or  sero-purulent. 

The  amount  of  effusion  is  usually  moderate,  but  there  may 

26 


402  .ETIOLOGY  AND  PATHOLOGY 

be  much  fibrino-plastic  exudation  on  the  visceral  and  parietal 
surfaces  of  the  pericardium,  and  in  exceptional  cases  a  large 
effusion. 

In  malignant  cases  of  rheumatic  pericarditis  there  is  great 
thickening  of  the  pericardium  and  the  inflammation  may 
spread  into  the  adjoining  mediastinal  tissues.  Nodular  masses 
of  necrosis  may  occur  in  the  parietal  layer,  and  large  deposits 
of  bloodstained  fibrino-plastic  exudation  are  found. 

In  a  third  form  the  process  is  slower  and  less  virulent  and 
results  in  a  gradual  fibrosis  of  the  pericardial  tissues  with 
complete  adhesion  of  the  pericardium.  Should  other  serous 
membranes  such  as  the  pleurae  and  peritoneum  be  then 
attacked  by  the  rheumatic  infection  the  syndrome  known  as 
multiple  serositis  may  develop.  This  condition,  however, 
would  seem  to  be  rare  in  rheumatism  and  to  be  much  more 
characteristic  of  tuberculous  pericarditis  in  which  the  much 
thickened  pericardium  strangles  the  heart  and  thus  produces 
one  of  the  great  factors  in  the  development  of  the  illness. 

It  is  from  the  pericardial  exudations  that  the  diplococcus  is 
most  easily  obtained,  doubtless  because  this  lesion  is  as  a  rule 
the  result  of  a  severe  attack. 

Endocarditis.  The  bacteria  are  carried  in  the  coronary 
circulation  to  the  neighbourhood  of  the  valves  and  as  in  peri- 
carditis produce  various  results.  We  find  them  in  the  suben- 
dothelial  tissue  causing  cell  proliferation  and  necrosis  with  the 
formation  of  minute  projections  from  the  margins  of  the  cusps 
which  become  later  the  vegetations.  These  are  firmly  attached 
to  the  substance  of  the  valve,  gradually  merging  into  the  normal 
structure.  Fibrin  may  or  may  not  be  deposited  upon  these 
vegetations  which  when  they  heal  do  so  by  the  usual  process  of 
fibrous  tissue  formation.  In  acute  rheumatism  active  endo- 
carditis of  the  simple  type  is  not  fatal,  and  the  diplococci  are, 
as  we  should  expect,  not  as  a  rule  found  in  large  numbers  in 
the  cardiac  valves  but  are  rapidly  destroyed  just  as  they  are 
in  the  walls  of  the  vermiform  appendix.  When  acute  rheu- 
matism proves  fatal  from  carditis  the  valvular  lesions  are 
usually  quieting  down,  and  they  are  difficult  structures  to  take 
cultures  from  without  contamination,  even  by  the  method  of 
reinforcement.  Various  investigators  have,  however,  con- 
firmed our  demonstration  of  them  in  these  tissues,  and  have 
isolated  them  from  the  vegetations. 


AETIOLOGY  AND  PATHOLOGY  403 

When  the  rheumatic  process  is  malignant  the  vegetations 
contain  great  numbers  of  the  diplococci,  and  the  areas  of 
necrosis  are  much  more  extensive.  The  obvious  lesions  may 
then  spread  some  distance  from  the  cardiac  valves  and  may 
in  the  case  of  the  aortic  and  mitral  valves  spread  from  the  one 
to  the  other  by  direct  extension.  It  should,  however,  be 
remembered  that  experiment  has  shown  that  in  the  "  simple  " 
type  of  infection,  the  diplococci  are  to  be  found  under  the 
endothelium  lining  the  cardiac  cavities  in  the  neighbourhood 
of  the  valves,  but  they  produce  such  minute  lesions  as  to  be 
invisible  except  under  the  microscope. 

Between  the  frankly  "  malignant  "  and  the  "  simple  " 
forms  there  are  to  be  found  all  grades  of  severity  and  there 
are  left  in  many  vegetations  of  the  "  simple  "  type,  areas  of 
necrotic  tissue  which  we  look  upon  as  elements  of  danger 
for  the  future.  The  duration  of  the  activity  of  endo- 
cardial vegetations  is  a  subject  which  still  requires  further 
investigation. 

We  attach  much  importance  in  the  history  of  rheumatic 
heart  disease  to  the  presence  of  these  foci  of  necrosis  which 
have  not  completely  healed,  because  we  look  upon  them  as 
areas  of  danger  in  which  the  diplococci  probably  live  for  weeks, 
months  or  years. 

There  is  a  third  process  in  the  history  of  rheumatic  endo- 
carditis which  must  be  mentioned  and  that  is  a  slow  persistent 
one  producing  gradual  fibrosis  of  the  valve  segments,  chordae 
tendineae,  papillary  muscles,  and  valve  ring.  This  is  best 
exemplified  by  the  well-known  mitral  stenosis,  but  the  same 
order  of  change  may  be  met  with  in  the  tricuspid  valve  and 
sometimes  in  the  aortic  producing  stenosis  of  the  valvular 
apertures. 

This  insidious  inflammation  may  follow  upon  an  acute 
attack,  but  may  also  develop  from  the  first  and  year  after  year 
may  remorselessly  advance,  doing  irretrievable  damage,  with 
symptoms  of  the  very  slightest  to  give  us  warning  of  the  true 
state  of  affairs. 

The  myocardial  lesions  in  rheumatic  carditis  are  twofold. 
The  interstitial  which  have  been  already  described  in  the 
earlier  part  of  the  article  under  the  submiliary  nodules,  but 
which  may  also  in  our  experience  be  sometimes  considerably 
more  than  submiliary  in  size  and  the  lesions  of  the  muscle 


4o4  AETIOLOGY  AND  PATHOLOGY 

fibres  themselves,  which  are  also  focal  and  of  which  the  most 
definite  are  the  fatty  changes. 

The  extent  of  these  lesions  varies  in  different  cases  and  we 
must  beware  of  over-rating  their  gravity,  for  there  are  many 
cases  of  fatal  rheumatic  morbus  cordis  in  which  they  are  of 
only  slight  degree. 

It  is  in  the  virulent  cases  with  much  dilatation  that  they 
are  the  most  definite,  but  further  experience  both  of  the  morbid 
anatomy  and  clinical  history  of  rheumatic  carditis  is  needed  to 
establish  on  sure  ground  our  accurate  knowledge  of  these  lesions. 

It  is  in  this  direction  that  we  await  further  light  from  a 
study  of  arrhythmias  in  active  rheumatism  by  the  recent 
methods  of  electro-cardiography. 

In  any  consideration  of  the  myocardium  we  must  not  lose 
sight  of  the  implication  of  the  cardiac  nerves  in  the  focal 
lesions  and  of  damage  to  the  auriculo-ventricular  bundle  and 
its  ramifications. 

Extensive  fibrosis  of  the  myocardium  would  seem  to  us  to 
be  an  exceptional  event  in  rheumatic  heart  disease,  but  again 
upon  this  point  there  is  need  for  more  inquiry. 

The  rheumatic  infection,  although  it  may  produce  an 
arteritis  does  not  appear  to  damage  the  arteries  to  any  great 
extent  in  the  young,  and  in  older  subjects  it  is  difficult  to 
decide  when  there  is  extensive  arterial  change,  what  part,  if 
any,  the  actual  rheumatism  has  taken. 

Embolism  is  an  important  cause  of  arterial  damage,  and 
when  malignant  in  type  the  larger  arteries  may  as  a  result 
give  way  from  secondary  disease  in  their  walls,  or  again 
aneurysms  result. 

It  is  quite  possible,  though  incapable  of  proof,  that  some 
mild  degree  of  infection  of  the  vessels  may  occur  without  being 
of  any  clinical  importance,  but  among  results  possibly  a 
tendency  to  spasm  should  be  added. 

The  perivascular  fibrosis  that  occurs  in  the  numerous  lesions 
of  rheumatism  may  possibly,  when  extensive,  produce  some 
injurious  results  upon  the  circulation  by  curtailing  the  vascular 
supply  and  raising  the  blood  pressure,  but  it  is  a  result  that  it 
is  difficult  to  appreciate. 

Phlebitis,  as  one  of  our  earlier  papers  illustrates,  may,  in 
exceptional  cases,  be  severe  and  dangerous  to  life,  but  in  this 
country  it  is  not  recognised  as  a  frequent  occurrence. 


ETIOLOGY  AND  PATHOLOGY  405 

It  would  be  wearisome  to  repeat  in  detail  the  morbid  changes 
that  occur  in  every  organ  that  has  been  attacked  by  the  rheu- 
matic infection,  but  a  few  words  may  be  devoted  to  such 
important  ones  as  are  associated  with  the  nervous  system,  the 
respiratory  tract  and  the  kidneys. 

The  Nervous  System.  We  recognise  in  the  nervous  system 
as  we  do  in  the  heart  two  orders  of  lesion,  those  of  the  connec- 
tive tissue  and  of  the  nervous  tissue  proper  ;  but  the  general 
result  that  appeals  to  us  is  that  the  rheumatic  poisons  are  not 
very  actively  destructive  to  the  nervous  tissues  although  highly 
irritant. 

Diplococci  are  deposited  in  the  pia  mater  in  the  neighbour- 
hood of  the  minute  blood-vessels  and  set  up  the  usual  changes, 
among  them  the  formation  of  submiliary  nodules  as  recorded 
by  Fraenzel.  In  the  brain  the  diplococci  are  also  found  close 
to  the  minute  blood-vessels  in  the  connective  tissue  supporting 
them,  and  more  rarely  in  masses  in  the  neuroglial  tissue. 

Thrombosis,  perivascular  exudation  and  small  areas  of 
softening  occur  as  a  result  of  the  infection,  and  in  the  nerve 
cells  throughout  the  brain  there  result  the  evidences  of  a  toxic 
process  in  the  alterations  in  the  nuclei  and  tigroid,  and  the 
definite  but  slight  damage  to  the  medullated  nerve  fibres. 

The  meningeal  changes  recall  in  their  behaviour  the  sub- 
cutaneous nodule,  although  we  are  inclined  to  the  view  that 
in  rare  cases  an  acute  meningitis  may  result  as  recorded  in  one 
of  our  papers. 

It  seems  also  possible  that  in  the  exceptional  condition  of 
rheumatic  hyperpyrexia,  there  is  an  unusually  virulent  cerebral 
toxaemia  rather  than  an  overwhelming  invasion  of  the  cerebral 
tissues  by  the  diplococci.  Upon  this  point  our  evidence  is  at 
present,  however,  very  scanty. 

Interstitial  and  parenchymatous  changes  must  in  all 
probability  occur  in  all  parts  of  the  nervous  system  and  may 
well  explain  the  neuritic  pains  and  more  definite  symp- 
toms recognised  as  rheumatic  sciatica,  and  cervico-brachial 
neuritis: 

There  is  doubtless  more  to  be  learnt  in  the  future  as  to  the 
possibility  of  perivascular  fibrosis  in  connection  with  the 
nervous  system  producing  chronic  spinal  conditions  such  as 
disseminated  sclerosis,  and  as  to  whether  or  not  a  virulent 
rheumatism  may  not  also  in  exceptional  cases  damage  acutely 


406  AETIOLOGY  AND  PATHOLOGY 

the  nerve  tissue  itself.  A  certain  amount  of  clinical  evidence 
in  favour  of  such  possibilities  is  on  record. 

The  Respiratory  System.  The  Tonsils  have  attracted  great 
attention  and  with  good  reason,  for  there  can  be  no  doubt 
that  unhealthy  conditions  of  the  tonsils  and  naso-pharynx 
are,  especially  in  childhood,  closely  associated  with  acute 
rheumatism. 

The  direct  sequence  of  a  sore  throat  and  acute  rheumatism 
is  too  frequent  an  event  for  us  to  escape  from  the  conviction 
that  they  are  directly  associated. 

The  balance  of  evidence  at  the  present  time  favours  the  view 
that  in  angina  faucium  of  rheumatic  nature  there  is  a  rapid 
multiplication  of  the  strepto-diplococci.  The  pathological 
changes  in  the  tonsils  vary  with  the  virulence  and  chronicity 
of  the  processes.  Thus  acute  general  inflammation,  foci  of 
inflammation  with  follicular  exudation  or  a  fibrino-plastic 
exudation  may  be  met  with.  If  the  attacks  are  repeated 
enlargement  of  the  tonsils  results  and  in  their  depths  there  may 
be  foci  of  disease  with  areas  of  necrosis  which  are  hidden  from 
view.  We  have  found  such  areas  bound  down  under  the  scar 
tissue  of  an  amputated  tonsil.  Some  enlargement  with  tender- 
ness of  the  cervical  lymphatic  glands  is  frequent,  and  is  strictly 
analogous  to  the  enlarged  mediastinal  glands  that  are  found 
associated  with  severe  rheumatic  pericarditis.  Rheumatic 
infections  of  the  nasal  passages  and  naso-pharynx  require 
further  investigation. 

The  bacteriological  investigations  connected  with  these 
tonsillar  and  nasal  lesions  are  necessarily  difficult  on  account 
of  the  various  bacteria  that  are  to  be  found  in  these  structures, 
and  this  difficulty  has  undoubtedly  delayed  the  progress  of 
investigation. 

Rheumatic  affections  of  the  articulations  of  the  larynx  seem 
to  be  very  unusual,  at  least  in  childhood,  and  laryngitis  does 
not  appear  to  be  a  part  of  an  acute  rheumatism. 

Pleurisy  is,  however,  frequent,  and  is  almost  always  present 
in  the  worst  cases  of  rheumatic  carditis  in  childhood.  Usually 
it  is  a  "  dry  "  form,  but  there  may  be  sufficient  effusion  to 
demand  tapping,  and  then  a  sero-fibrinous  exudation  is  with- 
drawn, from  which  the  diplococcus  has  been  isolated  in  pure 
culture. 

The  question  of  an  isolated  infection  of  the  pleura  is  a  very 


ETIOLOGY  AND  PATHOLOGY  407 

difficult  one  to  express  an  opinion  upon.  Bronchitis  has  been 
thought  by  some  to  be  a  symptom,  but  we  have  no  facts 
bearing  upon  this  point. 

In  the  lungs,  apart  from  infarction,  we  recognise  two 
conditions,  a  broncho-pneumonia  and  an  acute  cedema. 

The  broncho-pneumonia  is  associated  with  the  presence  of 
numerous  diplococci  in  the  alveoli.  These  must,  it  is  clear,  be 
distinguished  from  the  diplococcus  lanceolatus.  The  exudation 
is  sero-fibrinous  and  there  is  often  a  good  deal  of  pulmonary 
collapse  around  the  pneumonic  areas .  In  virulent  cases  there  are 
sub-pleural  ecchymoses  and  also  haemorrhages  into  the  alveoli. 

Pulmonary  cedema  occurs  as  an  exceptional  event  in  the 
course  of  an  acute  rheumatic  carditis.  It  is  a  very  definite 
if  rare  lesion,  the  lungs  rapidly  becoming  cedematous  from 
above  downwards.  Whether  the  condition  is  directly  rheu- 
matic or  the  result  of  a  failing  circulation  or  of  depressing 
remedies  has  not  been  decided,  but  it  may  occur  without  any 
evidence  of  severe  renal  disease.  Sections  show  the  alveoli 
full  of  a  serous  exudation. 

In  the  kidneys  the  changes  produced  by  the  rheumatic 
infection  are  less  clearly  understood.  They  would,  however, 
appear  to  be  of  much  the  same  character  as  in  other  organs  : 
thus  acute  nephritis  may  result  or  a  toxic  action  on  the  essential 
cells  may  cause  their  necrosis.  Infarctions  may  produce 
localised  areas  of  sclerosis,  and  judging  from  a  study  of  fatal 
cases  of  mitral  stenosis,  a  general  renal  sclerosis  may  also 
occur.  This  has  been  also  described  by  Drs.  Cowan  and 
Fleming,  who  consider  it  to  be  the  result  of  various  causes.  In 
1905,  in  Osier's  and  Macrae's  system,  we  gave  some  clinical 
and  experimental  facts  which  support  the  view  that  the 
stenosis  of  the  mitral  valve  and  sclerosis  of  the  kidneys  may  be 
both  of  rheumatic  origin.  The  diplococcus  can  be  isolated 
from  the  urine  in  virulent  cases  of  acute  rheumatism. 

The  pathology  of  the  alimentary  canal  in  rheumatism  is  a 
subject  but  little  understood  and  yet  of  great  interest.  All 
medical  men  are  acquainted  with  the  view  that  rheumatism 
may  be  the  result  of  auto-intoxication  from  the  bowel,  and 
many  believe  that  there  may  be  a  direct  infection  from  the 
bowel,  as  there  may  be  from  the  tonsils. 

At  present  the  facts  ascertained  about  appendicitis  are 
perhaps  the  most  accurate  at  our  command. 


408  ETIOLOGY  AND  PATHOLOGY 

We  know  that  the  diplococcus  isolated  during  life  from  a 
case  of  acute  rheumatism  may,  on  intravenous  inoculation, 
produce  appendicitis  of  varying  severity  in  young  rabbits. 
We  also  know  that  a  diplococcus  obtained  from  a  follicular 
tonsillitis  in  a  child  has  been  isolated  from  an  appendix  which 
was  also  simultaneously  in  a  state  of  inflammation,  and  that 
the  diplococcus  produced  appendicitis,  arthritis  and  endo- 
carditis in  young  rabbits. 

Our  later  investigations  have  shown  the  close  pathological 
resemblance  between  the  changes  in  the  animal  and  human 
appendices,  and  led  us  to  recognise  dilatation  of  blood-vessels, 
necrosis  of  tissue,  fibrino-cellular  exudation  and  leucocytosis, 
together  with  destruction  of  the  diplococci  by  the  living  tissues. 
The  chronic  changes  in  some  cases  of  recurrent  appendicitis  in 
man  are  comparable  to  those  in  chronic  rheumatic  arthritis, 
myocarditis,  pericarditis  or  endocarditis. 

These  pathological  results  have  this  particular  interest,  that 
they  show  that  an  intravenous  inoculation  may  produce  an 
appendicitis  and  an  arthritis,  or  an  arthritis  alone.  They  also 
illustrate  that  in  animals  the  association  of  an  arthritis  with 
an  intestinal  lesion,  does  not  by  any  means  prove  that  the 
arthritis  is  a  result  either  of  auto-intoxication  from  the  intes- 
tine or  even  auto-infection  by  that  route.  Evidence  of  this 
nature,  although  only  based  upon  animal  experiment  is  a  useful 
warning  to  us  to  accept  with  caution  dogmatic  assertions  that 
rheumatism  is  the  result  of  an  auto-intoxication  from  the 
bowel,  and  to  keep  before  our  mind  the  other  possibility  that 
alimentary  disease  and  arthritis,  when  co-existent,  may  both 
depend  upon  a  common  cause  arising  in  some  focus  distant 
from  either. 

The  pathology  of  the  alimentary  system  in  acute  rheumatism 
is  so  little  known  because  there  is  little  clinical  evidence  at 
present  pointing  to  severe  abdominal  affections  resulting  from 
the  disease.  Appendicitis  is  still  sub  judice ;  mucous  colitis  in 
rheumatism  is  not  fatal  and  the  other  abdominal  symptoms 
are  also  transitory,  although  gastric  symptoms  in  the  adult 
associated  with  dilatation  may  be  severe. 

In  concluding  this  section  we  must  allude  to  the  question  of 
dental  caries  and  gingivitis.  The  work  of  Mr.  Goadby  upon 
pyorrhoea  and  alveolarum  in  this  country  is  well  known,  and 
to  us  there  seems  to  be  a  wide  field  for  investigation  in  this 


ETIOLOGY  AND  PATHOLOGY  409 

direction.  Writing  with  the  greatest  caution  and  trusting 
solely  to  clinical  experience,  we  are  not  as  yet  convinced  that 
dental  disease  is  closely  associated  with  acute  rheumatism  in 
childhood.  Because  an  arthritis  may  arise  by  an  infection 
from  diseased  gums  this  does  not  necessarily  imply  that  acute 
rheumatic  arthritis  has  such  an  origin.  Further  study  of  the 
question  is  required,  and  in  the  future  no  doubt  more  evidence 
for  or  against  rheumatic  infection  through  the  gums  will  be 
forthcoming. 

This  general  outline  of  the  pathology  of  acute  rheumatism 
prepares  us  for  the  acceptance  of  the  fact  that  the  symptoms 
are  numerous  and  vary  greatly  with  the  virulence  of  the 
infection  and  the  extent  of  the  tissues  involved. 


SYMPTOMATOLOGY 

We  are  able  to  explain  the  clinical  symptoms  of  acute 
rheumatism  by  the  view  that  we  have  put  forward  with 
considerable  accuracy,  and,  we  think,  much  more  clearly  than 
is  possible  by  any  other  explanation  of  its  causation. 

Two  general  statements  can  be  made  upon  this  subject  of 
the  symptomatology.  The  first,  that  in  the  future  all 
descriptions  of  acute  rheumatism  will  be  probably  based  upon 
a  survey  of  the  disease  in  the  young,  and  such  peculiarities 
as  occur  in  adult  life  will  be  looked  upon  as  departures 
from  the  classical  disease  which  is  seen  in  its  truest  cha- 
racters in  childhood.  The  second,  that  the  symptoms  do 
not  always  combine  to  produce  an  acute  disease  running  a 
definite  course.  On  the  contrary  the  symptoms  may  not  only 
be  at  first  indeterminate,  but  they  may  even  occur  as  isolated 
events  pointing  to  the  implication  of  one  important  organ 
only.  Thus  there  may  be  a  characteristic  rheumatic  fever  or 
an  illness  with  numerous  equivocal  symptoms  which  at  last 
develop  and  betray  the  real  condition,  or  there  may  be  a 
solitary  carditis,  polyarthritis  or  chorea.  Any  description  of 
the  symptoms  of  acute  rheumatism  must  then  be  almost  as 
formidable  an  undertaking  as  a  description  of  tuberculosis. 

For  the  present  the  most  satisfactory  plan  would  appear  to 
us  to  give  first  an  outline  of  the  acute  general  disease  as  it 
occurs  in  the  young  and  the  adult,  and  then  to  give  the  symp- 
toms of  the  chief  local  manifestations  as  they  occur  under 
different  conditions  of  virulence  and  duration. 


Generalised  Rheumatism.  An  acute  severe  attack  in  a  child 
runs  somewhat  this  course.  After  a  more  or  less  definite 
history  of  a  chill  or  exposure,  a  sore  throat  develops  which  may 

410 


SYMPTOMATOLOGY  411 

be  red  and  relaxed,  or  may  be  a  follicular  tonsillitis  or  more 
rarely  a  tonsillitis  with  a  fibrino-cellular  membranous  deposit 
upon  the  surface.  There  are  malaise  with  fever,  pains  in  the 
joints  and  muscles,  and  prostration.  If  the  virulence  is  high 
vomiting  and  diarrhoea  may  usher  in  the  illness.  Several 
articulations  become  swollen  and  the  skin  over  them  may 
show  a  red  flush.  The  knees  and  ankles  among  the  larger 
joints  are  very  frequently  attacked  ;  but  the  smaller  joints  may 
suffer  also.  Pain  in  the  chest  directs  attention  to  the  heart, 
which  is  found  to  be  acting  rapidly  and  to  be  dilated,  and  later 
endocarditis  and  pericarditis  appear.  An  erythematous  rash 
may  be  noticed,  or  after  some  headache  choreic  movements 
develop  and  later  again  subcutaneous  nodules.  Anaemia  soon 
becomes  apparent,  and  within  three  weeks  it  is  clear  that 
the  child  is  the  victim  of  a  severe  attack  of  rheumatic 
fever. 

In  the  adult  the  acute  disease  described  so  definitely  in  all 
our  text-books,  does  not  appear  to  us  to  be  so  frequent  an 
occurrence  in  our  hospital  wards  as  it  did  twenty  years  ago. 
When  a  classical  example  occurs,  there  are  usually  the  same 
chilly  feelings  and  sore  throat  with  malaise,  prostration  and 
fever.  There  are  the  muscular  pains  also,  but  the  thickly 
coated  tongue,  profuse  sour-smelling  sweats,  rapid  and  severe 
polyarthritis  make  a  clinical  picture  so  striking  that  it  has  been 
thought  by  some  that  the  disease  is  not  identical  with  the  acute 
rheumatism  of  childhood.  Cardiac  affections  of  severity  are 
not  so  frequent,  but  dilatation  and  valvular  disease  are 
common  enough  in  the  adult. 

These  acute  cases  in  the  adult  are  usually  first  attacks. 
When,  however,  we  follow  the  history  of  rheumatic  children 
through  adolescence  into  adult  life,  it  becomes  apparent  that 
the  later  attacks,  though  often  not  so  severe  as  in  childhood, 
resemble  them  very  closely,  and  that  there  are  a  great  number 
of  examples  of  acute  and  subacute  rheumatism  which  are 
obviously  of  precisely  the  same  nature  as  those  that  occur  in 
childhood. 

The  peculiarities  that  we  notice  in  following  these  histories 
are  :  the  decreasing  tendency  to  develop  nervous  manifesta- 
tions, and  a  general  diminution  in  the  variety  of  symptoms  ; 
an  increasing  tendency  for  the  disease  to  linger  in  the  organs 
that   are  attacked  and  sometimes  with  this   chronicity  the 


4I2  SYMPTOMATOLOGY 

development  in  the  heart  of  malignant  forms  of  endocarditis 
and  in  the  joints  of  damaging  arthritis. 

The  peculiar  smouldering  type  of  the  rheumatic  process 
which  in  childhood  shows  itself  in  repeated  chorea  and  in  the 
early  stages  of  mitral  stenosis  becomes  very  apparent  in  the 
adult  female  in  the  severe  mitral  stenosis  so  repeatedly 
associated  with  repeated  attacks  of  mild  arthritis  and  muscular 
rheumatism. 

We  venture  to  think  that  the  influence  that  alterations 
in  the  tissues  from  age  and  habits  must  exert  upon  the 
behaviour  of  the  rheumatic  infection  has  not  yet  had  a  fair 
field  for  observation,  and  in  great  part  for  two  reasons  ;  the 
routine  description  of  rheumatic  fever  or  acute  rheumatism  as 
an  acute  process,  and  the  barrier  raised  to  a  broad  study  of 
the  disease  by  those  who  maintain  that  salicylate  of  soda  is  to 
be  the  criterion  of  a  rheumatic  lesion. 

The  exacerbations  of  the  disease  in  childhood  may  show 
themselves  in  the  development  of  different  manifestations. 
An  illness  commencing  with  polyarthritis  and  carditis  may 
quiet  down  and  then  chorea  develop,  or  nodules  commence  to 
appear.  In  the  adult  arthritis  is  the  most  constant  symptom, 
and  exacerbations  of  arthritis  are  the  most  frequent  events  in 
the  relapses. 

Course  of  acute  rheumatism.  If  we  were  asked  to  give  an 
account  of  the  course  of  tuberculosis  we  are  convinced  that  no 
one  would  expect  to  obtain  an  adequate  answer.  The  same  is 
equally  true  of  rheumatism.  There  is  no  one  who  can  confi- 
dently describe  the  course  of  rheumatism,  or  who  knows  when 
the  disease  is  cured  or  only  latent.  Clinical  experience  of 
tuberculosis  enables  us  to  predict  with  a  certain  amount  of 
accuracy  the  course  of  the  acute  generalised  disease,  or  on  broad 
lines  that  of  the  pulmonary,  abdominal  or  meningeal  form. 

So  too,  with  rheumatism,  we  know  with  some  degree  of 
certainty  the  course  of  some  of  the  chief  types  we  may  choose 
as  illustrations. 

Virulent  generalised  rheumatism  may  prove  fatal  in  the  first 
attack  or  be  imperfectly  recovered  from  after  many  months. 
Acute  rheumatic  fever  in  the  adult  may  be  completely  recovered 
from  after  many  weeks  or  leave  some  permanent  injury  to 
the  heart. 

Mild  attacks  in  the  child  and  adult  may  quiet  down  in  three 


SYMPTOMATOLOGY  413 

weeks.  The  course  of  rheumatic  arthritis  is  usually  favourable, 
of  rheumatic  heart  disease  only  partially  so.  Malignant  local 
lesions  are  either  dangerous  to  life  or  only  damaging  in  accord 
with  the  particular  organ  thus  attacked.  The  nervous  pheno- 
mena in  rheumatism  are  as  a  rule  transitory.  Thus  we  find 
ourselves  repeating  much  the  same  experiences,  differing,  of 
course,  in  detail,  as  those  that  are  met  with  in  tuberculosis,  in 
which,  too,  we  are  also  confronted  with  the  difficulty  of  deciding 
whether  the  disease  is  cured  or  only  latent. 

The  Symptoms  of  the  Local  Manifestations 

Arthritic,  muscular  and  fascial  inflammations.  The  pain 
and  swelling  need  but  little  comment  ;  they  are  less  severe 
in  childhood  and  the  pain  is  frequently  in  the  region  of  the 
tendons,  and  often  is  more  severe  when  there  is  little  or  no 
swelling  of  the  joints  themselves.  When  there  is  considerable 
periarticular  swelling,  whatever  the  age,  it  is  an  indication 
that  the  infection  is  obstinate  in  type  and  will  be  slow  in 
subsiding,  for  it  points  to  very  definite  infiltration  of  the 
capsules  of  the  joints  with  the  inflammatory  exudation.  Even 
in  the  young  if  this  subacute  process  persists  there  may  be 
some  damage  to  the  cartilages. 

Although  a  monarthritis  is  exceptional  it  may  occur  at  any 
age,  and  when  it  affects  the  right  hip  joint  may,  in  childhood, 
be  mistaken  for  appendicitis.  In  the  young  also  the  small 
joints  of  the  fingers  and  toes  may  be  prominently  affected,  and 
spindle-shaped  swellings  result  in  consequence.  Muscular 
wasting  may  also  be  very  definite  if  the  arthritis  is  unusually 
severe  and  prolonged  in  duration. 

Bursas  may  be  implicated  and  ganglionic  swellings  appear  in 
connection  with  the  sheaths  of  the  tendons. 

Again  in  the  young  obstinate  cervical  arthritis  may  occur, 
simulating  very  closely  spinal  caries  and  in  rare  cases  resulting 
in  spondylitis. 

Realising  these  varieties  in  the  arthritis  in  the  young  at  an 
age  when  these  structures  are  untried  by  constant  wear  we 
cannot  but  believe  that  in  the  elderly  adult  acute  rheumatism 
may  produce  all  forms  of  arthritic  damage. 

Fibrositis  is  much  less  frequent  in  the  young,  but  it  is  well 
recognised  as  a  lumbago,  or  even  a  general  stiffness  such  as 
we  associate  with  the  elderly.     These  lesions  are  sometimes 


414  SYMPTOMATOLOGY 

very  puzzling  when  strictly  localised,  persistent  pain  in  the 
heels  may  suggest,  for  example,  tuberculosis  of  the  os  calcis, 
and  stiff  neck  caries  of  the  spine.  It  is  probable  that  some  of 
the  obscure  abdominal  pains  in  rheumatic  children  are  also 
the  result  of  a  fibrositis  in  the  lower  intercostal  or  abdominal 
muscles.  A  mild  periostitis  around  the  inflamed  joints,  par- 
ticularly the  knee-joints,  is  met  with  in  some  cases,  often  in 
association  with  subcutaneous  nodules,  and  it  may  also  occur 
in  the  form  of  a  local  node  at  a  distance  from  a  joint. 

The  subcutaneous  nodules  are  now  thoroughly  recognised  and 
have  been  found  in  young  adults  as  well  as  in  children,  although 
they  are  unusual  after  puberty.  Their  situation  over  bony 
prominences  and  along  tendon  sheaths  needs  no  further 
comment.  They  are  curiously  painless  and  vary  very  much 
in  size  and  duration.  Although  a  rule  with  exceptions,  their 
occurrence  is  usually  associated  with  heart  disease.  Some- 
times when  all  other  symptoms  appear  to  be  in  abeyance  these 
nodules  commence  to  appear  in  various  situations,  and  such 
an  event  always  indicates  the  danger  of  some  more  serious 
manifestation  arising.  When  chorea  develops  during  this 
phase  it  is  tempting  to  believe  that  similar  painless  nodules  are 
developing  in  the  meninges. 

Purpura  may  occur  round  a  nodule  and  in  rare  instances 
become  a  little  tender.  The  nodule  attaches  itself  to  the  skin, 
but  never  seems  to  produce  more  than  a  slight  dull 
redness.  The  rule,  however,  is  for  the  skin  to  move  freely 
over  them  and  to  remain  natural  in  colour. 

In  malignant  endocarditis  we  have  seen  large  nodules  and 
have  demonstrated  the  diplococci  in  their  dilated  blood-vessels, 
but  such  nodules  are,  we  believe,  rare. 

These  lesions  must  be  distinguished  from  the  minute  tender 
swellings  which  are  frequently  noticed  in  chronic  cases  of 
malignant  endocarditis  at  the  finger  ends  and  sometimes 
elsewhere  (Osier's  sign).  These  are  of  the  nature  of  minute 
emboli,  in  terminal  blood-vessels. 

The  cardio-vascular  manifestations.  These  are  cardiac  dila- 
tation, endocarditis  and  pericarditis,  the  most  characteristic 
clinical  conditions  being  a  general  carditis. 

The  symptoms  of  the  early  acute  cardiac  dilatation  namely  : 
a  quickened  low  pressure  pulse  ;  a  feeble  impulse  displaced 
outwards  ;    an  enlarged  deep  cardiac  dullness  ;  and  a  short 


SYMPTOMATOLOGY  415 

first  sound  at  the  apex  with  or  without  a  soft  systolic  bruit, 
coupled  with  an  accentuated  pulmonary  second  sound  at  the 
base,  deserve  the  closest  attention.  They  are  the  first  danger 
sign,  and  although  unfortunately  mitral  endocarditis  is  fre- 
quently associated,  it  is  certain  that  this  dilatation  may  appear 
and  subside  leaving  no  damage  behind. 

Acute  pericarditis.  This  is  the  lesion  of  the  heart  which, 
particularly  in  the  adult,  is  most  often  associated  with  obvious 
signs  of  cardiac  injury.  Precordial  pain,  breathlessness, 
pallor,  vomiting,  fever  and  delirium  may  all  occur.  Yet  in 
the  child  the  symptoms  may  be  few.  Pericardial  friction  and 
a  diffuse  and  excited  impulse  are  very  frequent  signs,  but  it  is 
exceptional  for  the  effusion  to  be  so  great  as  to  demand  para- 
centesis, and  in  our  experience  such  an  event  is  very  rare.  This 
lesion  points  to  a  grave  infection  and  it  is  by  far  the  most 
frequent  cause  of  death.  Nevertheless  pericarditis  usually 
proves  fatal  by  supervening  in  a  case  in  which  the  heart  has 
already  been  damaged,  and  though  a  first  attack  may  prove 
fatal  it  is  unusual.  We  must  remember  that  a  pericarditis  may 
be  chiefly  limited  to  the  back  of  the  heart  and  is  then  very 
difficult  to  detect.  Endocarditis  is  almost  always,  but  not 
invariably  associated. 

Acute  endocarditis  of  the  simple  type  gives  rise  at  first  to 
very  few  symptoms,  although  some  rise  of  temperature  is 
frequent.  The  mitral  valve  is  the  most  frequently  attacked 
and  next  the  mitral  and  aortic  valves.  This  latter  lesion  has 
not  attracted  sufficient  attention  in  the  young.  It  is  not  only 
a  frequent  occurrence,  but  a  very  serious  one.  Both  valves 
may  be  attacked  in  the  same  illness,  but  more  often  the  aortic 
is  involved  the  later,  and  should  this  lesion  then  predominate 
the  outlook  is  not  good.  A  pure  aortic  regurgitation  is  rare 
in  childhood  but  may  occur  as  it  does  also  in  experimental 
heart  disease. 

The  study  of  the  morbid  changes  prepares  us  then,  to  realise 
that  the  heart  disease  of  rheumatism  may  become  established 
in  the  young  with  very  little,  if  any,  clinical  evidence  of  its 
occurrence.  We  have  only  to  picture  the  minute  lesions  of  a 
mitral  endocarditis  to  see  how  probable  this  must  be.  When 
the  injury  is  a  chronic  one  of  the  nature  of  a  mitral  stenosis 
and  the  only  organ  attacked  the  heart,  can  there  be  any 
wonder  that  we  are  repeatedly  meeting  with  cardiac  lesions  of 


4i6  SYMPTOMATOLOGY 

mysterious  origin  ?  Experience  indeed  teaches  us  that  we 
often  relv  for  the  detection  of  rheumatic  heart  disease  upon 
the  warnings  given  us  by  such  other  manifestations  as  arthritis 
and  chorea.  We  do  not  mean  to  imply  that  with  a  severe 
carditis  there  are  not  very  definite  indications  in  precordial 
pain,  breathlessness,  pallor  or  cyanosis,  and  general  wasting, 
but  we  are  anxious  to  direct  attention  to  the  great  difficultv 
we  have  in  approaching  the  problem  of  the  prevention  of 
rheumatic  heart  disease  on  account  of  the  few  clinical  signs 
that  may  present  themselves.  In  the  adult  the  myocardial 
damage  produces  symptoms  much  more  constantly  and  rapidly, 
and  the  severe  results  of  an  acute  pericarditis  are  thoroughly 
recognised. 

We  would  repeat  that  the  insidious  way  in  which  at  an  early 
age  the  mitral  and  aortic  valves  may  both  be  damaged  is  a 
clinical  fact  which  should  always  be  before  our  minds. 

The  myocardial  damage  is  of  great  practical  importance,  and 
for  the  last  ten  years  we  have  repeatedly  directed  attention  to 
a  particular  group  of  rheumatic  cases  in  childhood,  in  which, 
together  with  breathlessness  and  general  nervousness,  the 
heart  remains  dilated  and  the  pulse  excitable  and  irregular, 
but  there  is  no  sign  of  a  valvular  lesion  or  at  the  most  a  soft 
systolic  murmur  audible  at  and  internal  to  the  left  nipple. 

Such  cases  are  obstinate  and  easily  break  down  under  strain. 
In  adults  the  same  condition  is  met  with,  and  rheumatism  is 
one  of  the  causes  of  those  dilated  irregular  hearts  which  are  so 
adversely  influenced  by  alcoholism  or  undue  physical  or  mental 
strain. 

Death  from  acute  dilatation  of  rheumatic  origin  is  very  rare, 
but  such  cases  investigated  by  Dr.  S.  West  and  Sir  James 
Goodhart,  gave  us  in  this  country  some  of  the  first  important 
facts  upon  myocardial  disease  in  rheumatism. 

The  chronic  forms  of  progressive  rheumatic  heart  disease  are 
represented  by  mitral  stenosis,  and  the  rarer  aortic  and 
tricuspid  stenosis  by  chronic  myocarditis  and  chronic  relapsing 
pericarditis.  The  severe  types  of  infection  are  recognised  in 
the  virulent  carditis  of  childhood.  The  healed  lesions  of  the 
heart  are  represented  by  chronic  heart  disease  and  adherent 
pericardium. 

One  condition  stands  out  as  a  special  one  by  reason  of  the 
peculiar  relation  of  the  lesions  to  the  general  blood  stream, 


SYMPTOMATOLOGY  4I7 

this  is  the  subacute  malignant  form  of  rheumatic  endocarditis 
The  morbid  anatomy  shows  us  necrotic  tissue  and  blood  clot 
full  of  the  diplococci,  projecting  into  the  blood  current  within 
the  heart,  and  clinical  observation  provides  the  symptoms  that 
must  result  from  the  general  dissemination  of  the  infective 
agent  either  alone  or  with  loosened  clot  or  necrotic  vegetation 
There  result  :   general  constitutional  disturbances  more  or  less 
paroxysmal,  in  accordance  with  the  liberation  of  the  infection 
into  the  general  circulation  and  evidenced  by  fever,  sweatings 
and  possibly  rigors  and  diarrhoea  :   local  lesions  the  result  of 
emboli,  which,  if  minute,  produce  purpura  or  nodosites  cutanees 
ephemeres  (Osier's  sign),  and  if  larger,  emboli  in  various  organs 
or  vessels. 

In  addition  to  these  cases  others  are  met  with,  which,  after 
showing  some  of  the  signs  of  malignant  endocarditis  over 
periods  of  several  months,  eventually  quiet  down  leaving  the 
heart  grievously  damaged. 

Arteritis  is  extremely  rare  as  a  clinical  feature  in  acute 
rheumatism,  the  occasional  changes  that  are  found  in  the  first 
part  of  the  aorta  giving  rise  to  no  symptoms  during  life.  On 
the  other  hand  we  have  seen  from  time  to  time  arterial  spasm 
with  the  phenomena  of  Raynaud's  disease,  including  local 
gangrene,  follow  upon  an  acute  carditis,  the  first  signs  showing 
themselves  within  six  months  of  the  cardiac  attack. 

Phlebitis.  The  nature  of  the  symptoms  are  well  illustrated 
in  our  paper  (No.  VI)  upon  this  subject,  in  the  first  part  of  this 
book. 

The  nervous  manifestations  of  rheumatism  are  among  the 
most  interesting  of  all  the  phenomena.  Chorea  stands  out  as 
the  landmark,  but  the  pathology  of  the  disease  prepares  us  to 
expect  that  there  may  be  often  enough  signs  of  disturbance 
which  stop  short  of  a  declared  chorea,  or  may  antedate  it  for 
some  weeks. 

Of  these  signs  those  of  cerebral  irritability  and  headache 
with  mental  and  psychical  instability  are  the  chief.  The 
choreiform  movements  may  be  slight  or  extremely  severe, 
acute  or  gradual  in  onset,  and  transitory  or  very  prolonged  in 
duration.  The  pathological  evidence  that  many  of  the  nerve 
cells  are  affected  by  the  poisons,  is  amply  borne  out  in  the 
clinical  study  of  chorea.  The  extent  of  disturbed  movement 
including,  as  Dr.  Langmead  has  shown,  nystagmus,  and  the 

27 


4i8  SYMPTOMATOLOGY 

psychical  and  intellectual  disorder  are  sufficient  proofs  of  this 
statement.  The  paralytic  type  may  almost  merge  into  a 
definite  embolic  hemiplegia,  and  suggests  in  some  cases  an 
abrupt  focal  invasion  of  the  tissues  by  a  considerable  number 
of  diplococci.  Of  great  interest  is  the  fact  that  though  the 
cerebral  tissues  do  not  seem  to  suffer  very  severely  in  the 
rheumatic  injuries  they  show  great  difficulty  in  throwing  off 
the  effects.  We  see  also  very  clearly  the  influence  of  predis- 
posing factors  in  the  powerful  effects  of  fright,  and  cerebral 
strain  in  predisposing  to  the  onset  of  chorea,  and  again  we 
recognise  that  this  form  of  rheumatism  is  very  closely  associated 
with  the  insidious  lesion  of  mitral  stenosis  and  shares  with  it 
its  tendency  to  attack  females. 

The  rheumatic  origin  of  chorea  receives  interesting  support 
from  our  recent  figures. 

In  217  cases,  122  gave  evidence  of  heart  disease  and  other 
rheumatic  manifestations.  In  twenty-eight  more  there  were 
arthritic  and  muscular  pains  ;  in  twenty-two  more  cardiac 
dilatation.  Ten  more  followed  a  sore  throat.  Twenty  of  the 
remainder  gave  no  history  of  any  cause,  but  two  of  them  later 
developed  acute  rheumatism.  Fifteen  were  attributed  to 
fright  and  shock,  but  in  some  of  these  no  direct  relation  could 
be  traced,  and  they  were  certainly  rheumatic  in  later  life. 
Eight  were  directly  attributed  to  strain  at  school. 

The  remarkable  decrease  of  chorea  after  puberty  suggests 
that  in  the  adult  a  search  for  rheumatic  cerebral  symptoms 
may  in  the  future  discover  that  the  disease  still  retains 
more  influence  upon  the  nervous  system  than  we  perhaps 
recognise. 

Rheumatic  hyperpyrexia  needs  no  description  here  for  it  is 
recorded  with  detail  in  all  the  leading  text-books.  The  condi- 
tion points  to  a  virulent  process,  but  the  actual  facts  at  our 
disposal  are  so  scanty  as  to  make  it  unwise  as  yet  to  offer  any 
further  suggestion  than  that  it  represents  some  peculiar 
virulence  rather  than  an  overwhelming  degree  of  infection  with 
the  diplococci.  The  signs  of  meningitis  and  of  the  rare  spinal 
lesions  are  in  no  way  peculiar. 

Rheumatic  neuritis  is  a  very  painful,  and  for  this  reason 
important,  result  of  rheumatism,  and  one  much  more  prominent 
in  the  adult.  The  symptoms  depend  upon  the  particular 
nerves  affected,  but  in  all  cases  pain  is  the  striking  event. 


SYMPTOMATOLOGY  419 

Respiratory  system.  Passing  mention  must  be  made  of 
epistaxis  which,  as  Dr.  S.  Phillips  has  pointed  out,  is  not  infre- 
quent in  rheumatic  children,  and  may  be  among  the  first 
warnings  of  an  attack.  It  is  sometimes  profuse,  but  repeated 
attacks  rather  than  a  single  severe  one  are  more  usual.  It 
may  be  associated  with  a  tendency  to  develop  bruises  on  slight 
injury  and  other  signs  of  a  hsemorrhagic  tendency. 

The  importance  of  tonsillitis  has  been  insisted  upon,  and  to 
this  we  must  add  the  danger  of  chronic  unhealthy  large  tonsils 
in  the  rheumatic. 

Though  we  are  so  convinced  of  the  importance  of  the  tonsils 
as  an  avenue  of  infection,  we  are  alive  to  the  fact  that  even 
enucleation  does  not  prevent  further  attacks  of  acute  rheu- 
matism. The  exact  value  of  this  operation,  and  it  is  the  only 
rational  one  in  our  opinion,  has  still  to  be  estimated  by  a 
laborious  collection  of  statistical  facts. 

The  general  impression  we  have  gained  up  to  the  present 
time  is  that  the  removal  of  these  unhealthy  tonsils  improves 
the  general  health  and  diminishes  the  liability  to  attacks  of 
sore  throat.  It  is  not,  however,  surprising  when  we  realise  the 
minute  size  of  these  diplococci  that  even  when  the  tonsils  have 
been  removed,  sore  throats  may  occur,  for  there  is  ample 
opportunity  for  the  micrococci  to  flourish  in  the  faucial  tissues 
or  in  the  hypertrophied  mucous  membrane  of  the  naso-pharynx, 
and  in  such  cases  we  have  seen  a  diffuse  red  flush  over  the  soft 
palate  and  around  the  pillars  of  the  fauces.  Some  tenderness 
and  swelling  of  the  cervical  lymphatic  glands  is  frequently 
complained  of  by  the  rheumatic. 

One  of  the  most  frequent  combinations  of  symptoms  in  acute 
rheumatism  is  sore  throat,  arthritis  and  morbus  cordis,  and  in 
severe  cases  the  rheumatic  symptoms  appear  within  a  week 
from  the  commencement  of  the  sore  throat. 

Rheumatic  pleurisy  is  frequent  in  severe  cases  of  cardiac 
rheumatism,  and  often  accounts  for  some  of  the  thoracic 
pain  in  the  attacks.  Pieuro-pericarditis  also  is  not  uncommon. 
In  only  exceptional  cases  is  there  sufficient  sero-fibrinous 
exudation  to  require  paracentesis. 

An  unusual  and  abrupt  rise  of  temperature  in  the  course  of 
an  attack  of  rheumatism,  though  always  suggesting  the 
possibility  of  hyperpyrexia,  may  be  also  the  result  of  a  rheu- 
matic broncho-pneumonia.     This  lesion  is  accompanied  by  a 


42o  SYMPTOMATOLOGY 

good  deal  of  alveolar  collapse  around,  and  may  thus  give  rise 
to  very  definite  signs  of  pneumonia,  although  the  actual  area 
involved  is  usually  small.  In  virulent  cases  there  may  be 
numerous  patches  of  this  kind. 

Acute  pulmonary  oedema  we  have  only  seen  with  severe 
carditis.  Sharp  rales  appear  over  the  upper  parts  of  the  lungs, 
and  spreading  rapidly  may  involve  all  the  lobes.  Lividity, 
rapid  breathing  and  heart  failure  usually  develop,  but  with 
free  stimulation  and  the  administration  of  atropine  there  may 
be  an  arrest  in  the  spread  of  the  oedema,  and  recovery  may 
follow.  The  proof  of  this  lesion  rests  on  careful  post-mortem 
and  microscopic  investigations,  but  it  is  certainly  a  very  rare 
event,  which  we  ourselves  have  only  met  with  in  childhood. 

Although  Hirsch  and  others  have  recorded  rheumatism  of 
the  crico-arytenoid  joints  with  laryngitis  we  have  not  had  an 
opportunity  of  observing  such  a  case  and  have  not  been  able 
to  recognise  with  certainty  a  rheumatic  bronchitis. 

The  thyroid  has  attracted  considerable  attention  in  acute 
rheumatism,  but  definite  facts  are  difficult  to  obtain.  Thyroid- 
itis has  been  recorded,  and  we  have  occasionally  seen  some 
fullness  with  tenderness  of  the  gland  during  chorea  in  child- 
hood. The  association  of  exophthalmic  goitre  with  a  previous 
history  of  rheumatism  is  well  recognised,  but  it  is  difficult  to 
trace  the  sequence  of  events.  We  have  never  seen  any  case 
of  this  kind  arise  in  childhood  during  or  after  acute  rheumatism. 

Ocular  changes.  The  chief  lesions  are  conjunctivitis,  both 
erythematous  and  phlyctenular,  and  iridocyclitis,  which  is 
certainly  rare. 

Cutaneous  manifestations.  These  may  occur  before  the  full 
picture  of  the  disease  has  developed  or  during  the  attack,  or 
as  an  almost  solitary  incident  between  definite  attacks. 

Erythemata,  scarlatiniform,  or  more  blotchy  in  character 
are  not  infrequent.  Sometimes  they  are  very  transitory  and 
curiously  localised,  at  other  times  diffuse,  and  then  may  last 
for  some  days.  In  the  generalised  cases  the  eruption  is  often 
multiform,  and  some  areas  of  it  may  be  by  no  means  unlike  a 
tinea  circinata  or  erythema  iris.  Blotchy  eruptions  on  the 
face  may  be  difficult  of  diagnosis  if  the  history  of  the  case  is 
unknown.  Purpura  as  one  of  our  papers  illustrates  may  be 
severe  and  widespread,  but  the  occurrence  is  rare.  Purpuric 
eruptions  of  slight  severity  are  far  more  common,  and  every 


SYMPTOMATOLOGY  421 

gradation  from  an  erythema  to  a  purpura  may  be  noticed  in  a 
single  case.  Heat  applied  to  a  rheumatic  erythema,  or  the 
stress  of  gravity  upon  the  dilated  capillaries  may  convert  such 
an  erythema  into  a  purpura.  Branny  desquamation  may 
follow  the  most  acute  erythemata. 

Psoriasis  appears  to  us,  as  it  did  to  the  late  Dr.  Crocker,  to 
bear  some  relation  to  rheumatism,  and  may  possibly  represent 
the  more  chronic  type  of  rheumatic  manifestation  in  the  skin. 
Bullous  eruptions  are  rare,  herpetic  ones  rather  more  frequent. 
It  is  worth  consideration  whether  the  so-called  sudaminal 
eruption  is  not  in  reality  a  rheumatic  manifestation. 

Erythema  nodosum  is  a  condition  of  much  interest  and  one 
about  which  there  is  no  agreement  as  to  causation.  It  may 
occur  in  the  rheumatic  and  it  may  also  occur  in  those  who  have 
never  had  rheumatism.  Whether  it  is  a  special  disease  allied 
to  acute  rheumatism  or  whether  it  is  an  outcome  of  many 
different  infections,  including  among  these  the  rheumatic,  is 
not  decided. 

Scleroderma  is  occasionally  met  with  after  an  attack  of 
rheumatic  fever. 

The  blood  is  much  damaged  by  virulent  rheumatism  and  the 
late  Dr.  Cheadle  frequently  pointed  out  that  in  childhood  it 
suffered  almost  as  much  in  this  disease  as  in  severe  diphtheria. 
There  is  a  rapid  fall  in  the  number  of  red  cells,  and  the  count 
may  remain  very  persistently  low.  A  moderate  leucocytosis 
may  also  occur.  The  diplococcus  can  be  isolated  from  the 
blood  in  virulent  cases,  and  we  have  demonstrated  their 
presence  in  the  polymorphonuclear  leucocytes. 

Nephritis  and  other  renal  lesions  deserve  notice.  The  acute 
condition  is  generally  transitory  ;  but  there  is  a  persistent 
form  associated  with  some  cases  of  malignant  rheumatic 
endocarditis  that  seems  to  us  to  require  more  attention  than 
it  has  received.  There  may  also  be  transient  albuminuria. 
Further,  our  experimental  investigations  show  that  renal 
infarction  may  occur  with  no  visible  endocardial  lesions,  which 
raises  the  question  as  to  whether  our  present  views  on  the 
pathology  of  infarction  are  not  somewhat  too  rigid  in  their 
conception. 

The  association  of  chronic  renal  disease  with  mitral  stenosis 
has  already  been  alluded  to,  and  also  needs  further  investigation. 
In   twenty    fatal    cases    of    mitral    stenosis,     all    of    which 


422  SYMPTOMATOLOGY 

showed  granular  kidneys,  the  age  limits  varied  between  19 
and  60  years,  and  seventeen  of  these  were  under  fifty  years 
of  age. 

The  abdominal  symptoms  in  rheumatism  are  another  field  for 
further  investigation,  and  at  present  difficult  to  write  upon 
with  any  confidence. 

Children  of  rheumatic  parentage  are  liable  to  attacks  of 
bilious  vomiting  with  white  constipated  stools,  and  at  the 
commencement  of  an  acute  attack,  vomiting  and  diarrhoea  with 
much  mucus  in  the  stools  may  occur.  Again,  between  attacks 
of  acute  rheumatism  mucous  colitis  may  develop.  In  adults 
severe  gastric  pain  with  vomiting  and  dilatation,  or  attacks  of 
pain  along  the  colon,  may  add  greatly  to  the  severity  of  the 
disease. 

What  relation,  if  any,  the  muco-membranous  colitis  of  the 
adult  bears  to  rheumatism  is  uncertain. 

We  isolated  the  diplococcus,  which  was  sometimes  growing 
in  great  numbers,  from  the  bile  in  infected  rabbits  on  more 
than  one  occasion,  but  heretofore  have  failed  with  cultures 
from  the  human  bile.  The  subject  is,  nevertheless,  worth  some 
further  consideration  as  having  a  possible  bearing  upon  the 
formation  of  gall-stones,  and  as  a  reminder  that  the  liver  may, 
for  all  we  know  to  the  contrary,  be  affected  by  the  rheumatic 
poisons. 

Beattie  has  directed  attention  to  the  precipitation  of  bile 
salts  by  the  diplococcus  in  vitro,  and  we  have  observed  the 
occurrence  of  a  large  gall-stone  in  a  rabbit  which  had  been 
inoculated  intravenously  with  this  micro-organism. 

Appendicitis  has  been  already  dealt  with  in  several  of  our 
papers,  but  the  clinical  points  of  chief  interest  at  the  moment 
are  as  to  whether  or  not  we  shall  in  the  future  be  able  to 
recognise  a  relapsing  rheumatic  form  of  the  affection,  or  whether 
the  relation  of  rheumatism  and  appendicitis,  so  clear  from 
animal  experiment,  does  not  hold  good  in  man. 

Peritonitis  undoubtedly  occurs  as  a  rheumatic  lesion,  but  it 
is  exceptional.  The  usual  symptoms  are  pain  in  the  upper 
half  of  the  abdomen,  and  loud  peritoneal  friction  may  be 
heard.  The  inflammation  is  usually  around  the  spleen  and 
over  the  liver,  but  cases  of  general  peritonitis  have  been 
described,  fibrinoplastic  in  character,  and  we  have  seen  general 
peritonitis  result  from  experiment. 


SYMPTOMATOLOGY  423 

Fever.  There  is  no  special  course  in  the  pyrexia,  but  there 
are  several  interesting  clinical  facts  about  the  fever  in  rheu- 
matism. The  remarkable  phenomenon  of  hyperpyrexia  is  the 
best  known,  but  it  is  very  rare  at  the  present  time,  and  in 
childhood  a  very  unusual  event  indeed.  Many  cases  of  rheu- 
matism run  a  course  of  moderate  fever  (102 °  F.)  terminating 
by  lysis  ;  others  may  show  many  recrudescences  extending  over 
weeks.  A  severe  lesion  such  as  pericarditis  or  a  pneumonia, 
may  cause  an  abrupt  rise,  but  this  is  seldom  alarming. 

The  virulent  cases  may  show  very  little  fever,  or  even  a 
subnormal  variation. 

There  are  cases  in  childhood  in  which  some  fever  may 
continue  over  many  weeks  with  no  obvious  clinical  sign  to 
account  for  it.  This  may  be  only  of  slight  degree,  but  experi- 
enced physicians  regard  this  fever  with  suspicion,  and  there  is 
no  sense  of  real  security  while  it  persists.  This  fact,  proved 
by  observation  in  hospital  wards,  is  of  particular  importance 
because  it  is  also  recognised  that  the  only  evidence  of  rheu- 
matism may  sometimes  be  a  mysterious  and  persistent  fever  ; 
and  the  definite  manifestations  only  appear  later. 

There  would  seem  to  be  room  for  further  observation 
upon  the  possible  effect  of  the  rheumatic  infection  upon  the 
re-productive  system. 

We  have  observed,  as  has  Dr.  Still,  mastitis  of  a  mild  form 
occurring  occasionally  in  girls  of  10  to  12  years  of  age,  who 
have  been  the  subjects  of  rheumatic  fever  ;  but  this  may  well 
have  been  a  coincidence.  Dysmenorrhea  of  an  acutely  painful 
nature  may  also  occur  in  girls  with  a  rheumatic  history,  yet 
this,  though  interesting,  is  only  suggestive,  and  may  quite  well 
be  independent  of  any  definite  lesions  of  a  rheumatic  kind. 

The  influence  of  the  finer fierium  upon  attacks  of  rheumatism 
has  seemed  to  us  to  be  detrimental  and  to  favour  the  develop- 
ment of  persistent  and  sometimes  malignant  lesions  of  the 
cardiac,  arthritic  and  nervous  systems. 

Attention  has  been  already  drawn  to  the  possible  influences 
upon  rheumatic  manifestations  of  altered  conditions  of  life 
and  surroundings,  faulty  habits  and  advancing  age. 


DIAGNOSIS  AND  PROGNOSIS 

(a)  DIAGNOSIS 

The  nature  of  the  rheumatic  infection  both  helps  us  to 
realise  and  prepares  us  for  the  difficulties  that  may  arise  in 
diagnosis.  The  micrococcus  is  itself  one  of  a  primitive  and 
large  group  of  bacteria,  with  close  allies  such  as  the  pneumo- 
coccus  and  more  septic  streptococci.  The  lesions  it  produces 
are  numerous  and  may  occur  in  groups  or  singly,  and  each  one 
may  be  mild  or  severe  in  character. 

It  is  easily  understood  then  why  many  have  claimed  that 
acute  rheumatism  is  not  in  reality  a  specific  disease  but  a 
result  of  various  infections  ;  but  none  the  less  we  hold  that 
this  view  is  mainly  held  by  those  who  have  limited  their 
observations  to  a  study  of  the  disease  in  the  adult.  Acute 
rheumatism  is,  in  fact,  one  of  the  most  specific  diseases  in  this 
country  ;  but  for  the  reasons  given  above  the  clinical  difficulties 
in  diagnosis  are  often  very  great. 

As  is  the  case  with  other  infections  the  diagnosis  is  most 
evident  when  the  complete  picture  is  presented  by  the  disease 
in  a  severe  attack  with  many  manifestations.  It  is  then  that 
we  recognise  the  association  with  tonsillitis,  the  liability  to 
cardiac  injuries,  the  absence  of  suppuration,  the  occurrence  of 
a  transient  painful  polyarthritis,  of  subcutaneous  nodules, 
erythemata  and  anaemia,  and  the  frequency  of  exacerbations. 

When  only  one  or  a  few  manifestations  are  present  or  when 
the  disease  is  unusually  prolonged  or  more  "  septic "  in 
character  doubts  may  arise. 

It  is  exceedingly  difficult  to  enumerate  all  the  possibilities 
of  error  in  the  diagnosis,  but  a  comparatively  easy  matter  to 
classify  them. 

A  solitary  symptom  such  as  pain  in  the  limbs  accounts  for 
many,  particularly  if  with  it  is  combined  the  practical  difficulty 

424 


DIAGNOSIS  425 

that  is  experienced  by  the  medical  man  in  meeting  the  demand 
of  the  public  for  a  name  for  all  disorders. 

Here,  for  example,  we  should  put  in  childhood,  scurvy,  osteo- 
myelitis and  anterior  poliomyelitis,  in  the  adult  the  lightning 
pains  of  locomotor  ataxy  or  neuritic  pains  of  carcinoma  of  the 
vertebrae.  With  the  mistake  of  relying  upon  one  sign  we  often 
find  we  have  coupled  that  of  imperfect  observation,  and  have 
missed  the  tender  swellings  of  scurvy,  the  extreme  illness  of 
osteo-myelitis  and  the  loss  of  reflexes  in  polio-myelitis. 

Another  source  of  numerous  errors  is  failure  in  realising  that 
there  are  many  infections  which  may  cause  a  particular  lesion 
such  as  arthritis,  and  that  the  clinical  signs  of  an  early  arthritis 
furnish  but  comparatively  crude  data  for  the  differentiation  of 
its  causation. 

Here  we  group  the  errors  of  mistaking  for  rheumatism, 
gonorrhceal,  septic,  tubercular,  pneumococcal,  syphilitic  and 
other  forms  of  arthritis.  This  is  an  error  all  the  more  easily 
made  because  the  term  rheumatism  is  used  vaguely,  sometimes 
for  a  special  disease  and  sometimes  for  a  transitory  arthritis. 
Here  again  imperfect  observation  encourages  error  from  the 
oversight  of  the  other  manifestations  of  each  of  these  diseases, 
some  of  which,  when  coupled  with  the  arthritis,  would  make 
the  diagnosis  clear. 

A  third  group  of  errors  arises  from  the  limitations  of  our 
knowledge.  This  is  illustrated  by  "rheumatoid  arthritis." 
Our  views  on  this  condition  are  even  now  in  a  state  of  chaos 
partly  from  a  lack  of  accurate  facts  about  the  bacteriology  and 
also  from  ignorance  of  the  possibilities  the  metabolic  changes 
in  the  tissues  themselves  may  possess  for  producing  disease 
without  the  aid  of  infection.  The  difficulties  are  increased  by 
the  continual  appearance  of  dogmatic  assertions  as  to  the 
nature  of  the  condition. 

It  is  clear  that  if  some  specific  test  could  be  found  for  the 
diplococcus,  the  problem  of  the  diagnosis  of  acute  rheumatism 
would  be  greatly  simplified. 

(b)  PROGNOSIS 

The  conception  of  acute  rheumatism  as  the  result  of  an 
infection  undoubtedly  gives  much  assistance  in  prognosis, 
for  when  we  accept  it,  we  naturally   find   ourselves   guided 


426  PROGNOSIS 

bv  the  rules  which  govern  our  thoughts  upon  infective  pro- 
cesses in  general.  We  attempt  instinctively  to  gauge  the 
virulence  of  the  infection  guided  by  the  clinical  evidences  of 
that  virulence,  and  we  also  pay  attention  to  the  individual 
attacked  ;  ascertain  his  family  history  and  apprise  his  power 
of  resistance  by  the  general  rules  which  guide  us  in  all  such 
inquiries.  Age,  surroundings,  and  other  predisposing  influences 
are  also  taken  into  account. 

Yet  these  general  indications  are  not  the  only  guides.  We 
have  also  the  assistance  afforded  by  the  study  of  the  infection  in 
those  organs  which  are  most  affected  in  the  particular  illness. 

It  is  clear  that  a  delicate  child  of  tender  age  with  a  strong 
hereditary  predisposition  to  the  disease,  who  is  struck  down 
by  acute  rheumatic  fever  with  severe  carditis  will  either  die  or 
be  so  crippled  that  in  the  future  the  health  will  be  greatly 
damaged. 

We  recognise  even  more  than  this,  however,  for  we  realize 
that  such  a  patient,  far  from  being  protected  from  future 
attacks  is  exceedingly  liable  to  them. 

On  the  other  hand,  a  strong  adult  with  an  attack  of  severe 
polyarthritis,  brought  on  by  exceptional  exposure  to  adverse 
influences,  will  in  all  probability  make  a  good  recovery,  and 
although  liable  in  the  future  to  renewed  attacks  may,  if  he  is 
prudent,  never  suffer  again. 

Again  we  are  brought  to  realise  a  very  difficult  problem  in 
the  prognosis  in  early  life  which  is  dependent  upon  the  tendency 
of  the  disease  to  recur.  This  turns  on  the  unfortunate  fact 
that  because  a  child  has  escaped  on  one  occasion  with  little  or 
no  damage  it  is,  nevertheless,  no  guide  as  to  the  possible 
severity  of  a  future  attack. 

This  problem  is  clearly  one  upon  which  in  the  future  per- 
sistent study  of  the  disease  as  a  result  of  infection  will  probably 
throw  light. 

We  are,  however,  not  only  guided  in  our  prognosis  by  the 
virulence  of  the  infection,  but  also  by  the  particular  character 
of  the  process.  When  the  chronic  smouldering  form  discloses 
itself,  as  for  example,  in  the  advent  of  a  mitral  stenosis,  we 
recognise  that  such  damage  as  has  been  done  is  permanent, 
and,  moreover,  exceedingly  likely  to  progress,  although  perhaps 
very  slowly. 

When  we  turn  to  the  particular  organ  affected,  with  the 


PROGNOSIS  427 

rare  exceptions  of  fatal  chorea  or  hyperpyrexia,  it  is  brought 
home  to  us  that  the  heart  is  the  great  danger  point.  Here 
again  we  gain  great  assistance  in  prognosis.  Severe  carditis, 
damaging  as  it  does  several  valves,  the  heart  wall  and  peri- 
cardium, must  always  be  grave.  Malignant  types  of  endo- 
carditis, by  virtue  of  their  peculiar  relation  to  the  general 
circulation,  are  nearly  always  fatal.  The  great  importance  of 
damage  to  the  myocardium  is  brought  home  to  us  as  a  common 
result  of  cardiac  infections,  and  we  can  understand  how  it 
may  be  that  a  simple  mitral  endocarditis,  which  would  seem 
to  be  the  least  dangerous  of  valvular  lesions  may,  nevertheless, 
run  a  most  disastrous  course  because  the  rheumatic  infection 
has  at  the  same  time  greatly  injured  the  cardiac  wall. 

The  influences  of  imperfect  convalescence,  poverty,  un- 
healthy surroundings  and  laborious  occupations  can  be 
thoroughly  realised  as  tending  to  cause  renewed  cardiac  injury. 

A  knowledge  of  the  morbid  changes  that  occur  in  arthritis 
speedily  makes  us  alive  to  the  gravity  of  persistent  inflamma- 
tion in  these  structures  and  helps  us  to  recognise  the  extent 
which  we  may  expect  the  limits  of  recovery  to  reach. 

So  also  our  knowledge  of  the  pathology  of  rheumatic  chorea 
lead  us  to  understand  the  recovery  which  we  may  expect, 
although  it  may  be  long  delayed. 

Enough,  we  think  then,  has  been  written  upon  this  question 
of  prognosis  in  rheumatism  to  make  it  apparent  how  helpful 
the  view  of  the  disease  we  have  put  forward  is  in  solving  its 
various  difficulties,  and  keeping  before  us  the  limitations  of 
our  knowledge. 


TREATMENT 

The  last  consideration  is  the  influence  of  these  researches 
upon  the  all-important  problem  of  the  treatment  of  the 
disease. 

As  we  have  stated  in  the  introduction,  no  dramatic  "  Cure  " 
has  appeared  to  encourage  us,  but  on  the  contrary  the  specific 
treatment  has  seemed  to  become  an  even  more  difficult 
problem  than  it  was  before  we  commenced  these  investigations. 
How  we  are  to  destroy  these  micrococci  in  the  tissues  without 
at  the  same  time  injuring  the  tissues  themselves  is  the  obvious 
difficulty  that  confronts  us,  and  is  the  greater  because  they 
may  have  gained  a  firm  hold  in  the  system  before  any  oppor- 
tunity of  coping  with  them  is  afforded.  Then,  owing  to  the 
extreme  difficulty  of  differentiating  the  members  of  the  strepto- 
coccal group,  and  the  difficulty  we  have  found  in  preserving 
the  virulence  of  the  diplococcus  in  vitro,  a  study  of  the  toxines 
has  been  an  undertaking  beyond  our  powers.  Further  clinical 
investigation  of  the  results  of  this  infection  has  brought  home 
to  us  the  extreme  subtlety  of  the  poisons  that  are  produced 
which  may  cause  prolonged  and  most  complex  results  in  such 
organs  as  the  brain,  where  the  clinical  results  can  be  so  clearly 
recognised. 

Many  of  the  methods  of  treatment  that  are  described  in  every 
text-book  can  be  readily  seen  to  be  rational,  such  as  rest,  the 
relief  of  pain,  the  combating  of  fever,  and  the  prolonged  con- 
valescence, for  they  are  measures  needful  in  the  treatment  of 
all  infections,  and  the  slow  convalescence  is  particularly  called 
for  by  the  peculiar  tendency  of  the  rheumatic  infection  to 
attack  the  heart.  Our  researches  obviously  suggest  great 
attention  to  sore  throat  during  the  illness. 

With  more  caution  as  to  the  interpretation,  the  employment 
of  the  alkalis  would  appear  to  be  of  value,  for  the  little  that 
is  known  of  the  poisons  produced  by  the  diplococcus  points  to 

428 


TREATMENT  429 

the  production  of  deleterious  acids  as  one  of  its  results  in  the 
tissues. 

The  great  problem  every  medical  man  meets  with  in  the 
matter  of  drugs  is,  we  need  hardly  state,  the  position  of  the 
salicyl-compounds  in  the  treatment  of  the  disease  ;  and 
upon  it  we  write  with  the  utmost  deference  to  the  opinions 
of  others.  No  thinking  man,  with  a  knowledge  of  the  ravages 
of  rheumatism  before  his  mind,  would  deliberately  attempt 
to  obstruct  any  method  of  treatment  of  this  disease  which 
promised  to  be  specific,  and  nothing  that  is  written  here 
should  be  looked  upon  as  an  expression  of  an  antagonistic 
attitude  to  those  who  are  not  in  agreement,  but  as  an 
expression  of  opinion  based  upon  what  appears  to  us  the 
present  evidence. 

To  us  it  has  seemed  astonishing,  when  we  bear  in  mind  the 
immense  experience  of  these  drugs  that  has  now  accumulated, 
that  the  specific  action  if  it  exists  has  not  yet  been  definitely 
established.  We  look  upon  a  specific  drug  as  one  which  pro- 
duces results  so  definite  and  incontestable  that  none  but  the 
blind  opponent  can  mistake  them.  Our  experience  has  been 
that  whether  very  large,  medium  or  small  doses  of  the  salicy- 
lates are  given  in  this  disease,  we  have  failed  to  discover  any 
such  striking  results.  We  would  put  a  clear  issue  forward  and 
state  that  if  ten  cases  of  acute  rheumatism  in  which  sub- 
cutaneous nodules  were  appearing  were  treated  by  any  doses 
of  these  drugs  that  a  physician  chose  to  venture,  and  ten  more 
were  treated  by  the  simple  alkalis,  the  result  would  be  that 
we  should  see  no  striking  difference  in  their  course  under  the 
two  methods.  That  is,  although  they  are  the  most  easily 
appreciated  and  most  characteristic  of  all  rheumatic  lesions,  we 
should  not  see  them  melt  away  under  the  salicylate  treatment 
and  linger  under  the  alkaline. 

We  cannot  deny  that  the  salicylates  relieve  pain,  and  lower 
the  temperature,  but  they  do  this,  it  must  be  added,  in  many 
other  conditions.  Aspirin  will  relieve  the  pain  of  cancer,  of 
tabes  dorsalis  and  of  influenza.  Salicylate  of  soda  will  ease 
the  pain  of  gout  and  of  early  suppurative  arthritis.  Whenever 
there  is  relief  of  pain  there  is  mental  and  bodily  rest,  and 
consequently  more  vital  power  for  the  natural  resistance  to 
diseased  processes. 

It  is  quite  possible  that  these  drugs  may  have  some  actual 


430  TREATMENT 

specific  influence  upon  the  rheumatic  poisons  formed  in  the 
processes  of  arthritis,  and  not  upon  the  poisons  formed  in 
different  tissues  such  as  the  brain  and  heart.  Even  this  point, 
however,  does  not  seem  to  stand  out  clearly,  for  it  is  remarkable 
how  rapidly  in  childhood  a  rheumatic  arthritis  will  subside 
when  only  rest  is  employed  ;  and  on  the  other  hand,  when  in 
an  adult  or  child  the  arthritis  is  of  the  stubborn  periarticular 
type,  how  the  salicylates  may  fail.  The  obvious  objection  that 
is  always  raised  is  that  these  latter  cases  are  not  rheumatic. 
We  can  only  state  that  our  experience  has  led  us  to  maintain 
that  they  are  undoubtedly  of  that  nature,  and  would  add 
that  we  believe  that  in  some  delicate  subjects  these  drugs, 
if  persisted  in,  do  actual  harm  by  producing  a  general  depres- 
sion of  the  resistance.  It  is  worthy  of  consideration  also, 
whether  these  drugs,  by  lowering  temperature  and  easing 
pain,  may  not  sometimes  lull  the  medical  man  into  a  sense  of 
false  security. 

We  would  wish  to  make  it  quite  clear  that  these  expressions 
of  opinion  are  concerned  only  with  the  specific  action  of  the 
salicylates.  We  realise  the  great  value  of  these  drugs  in  the 
treatment  of  rheumatism  and  look  upon  them  as  the  most 
valuable  that  we  possess,  and  even  think  that  they  may  have 
a  specific  action  on  some  one  of  the  rheumatic  poisons  ; 
but  fully  alive  as  we  are  to  their  value  we  would  point  out 
that  they  are  most  efficacious  in  those  cases  which  are  acute 
and  in  which  pain  and  suffering  with  fever  are  prominent, 
and  in  which  the  lesion  is  the  most  transitory  and  most 
easily  produced  of  all  the  rheumatic  manifestations,  namely 
polyarthritis. 

The  natural  conclusion  is  that  we  advocate  their  use  for  the 
polyarthritis,  muscular  pains,  or  headache  of  chorea,  but  do 
not  press  them  for  their  specific  action  in  heart  disease,  although 
prepared  to  do  so  tentatively  in  severe  polyarthritis.  We  do 
not  press  them  in  heart  disease  or  chorea,  because  not  being 
persuaded  of  their  specific  action,  we  are  convinced  from 
experience  that  they  may  produce  severe  vomiting,  general 
depression,  dizziness,  delirium,  air-hunger  and  even  fatal  coma. 
In  other  words  they  may  introduce  into  severe  cases,  added 
dangers  of  their  own  making. 

The  various  tonics  used  in  the  convalescent  stages  of  the 
disease  require  no  particular  comment,  except  that  the  digestion 


TREATMENT  431 

of  these  patients  is   by  no   means   always  satisfactory   and 
caution  is  needed  in  giving  the  iron  compounds. 

The  question  of  diet  is  an  interesting  one,  and  all  our  investi- 
gations go  to  show  that  in  childhood  it  takes  no  part  in  causa- 
tion of  the  disease.  We  have  entirely  abandoned  the  idea 
that  meat  is  harmful,  and  are  guided  only  by  the  general  rules 
for  the  diet  of  invalids  dependent  upon  their  powers  of 
assimilation,  the  stage  of  the  disease  and  the  occurrence  or  not 
of  complications. 

It  is  another  question  whether  persistent  errors  in  diet  may 
not  in  the  adult  deprave  the  tissues  and  allow  the  rheumatic 
infection  to  produce  lesions  which  are  more  locally  destructive 
than  in  the  child.  In  this  case  it  is  the  evil  habit  of  life  that 
has  altered  the  constitution  before  the  infection  has  attacked 
the  individual. 

The  treatment  by  vaccines  will,  in  this  country,  be  the  one  in 
which  we  should  expect  the  medical  profession  will  show 
particular  interest,  but  we  would  raise  a  mild  protest  against 
an  argument  that  has  been  raised  of  late,  that  failure  with  this 
method  is  strong  evidence  against  the  causal  nature  of  the 
diplococcus.  This  is  indeed  a  questionable  method  of  reason- 
ing, for  it  assumes  that  the  vaccine  methods  are  perfected  and 
that  their  method  of  action  is  well  understood.  Upon  these 
assumptions  obvious  and  indisputable  facts  of  experimental 
investigation  are  to  be  thrown  aside. 

By  this  method  of  treatment  good  results  and  negative 
results  have  been  recorded,  and  both  events  would  seem  to  be 
possible. 

It  must,  however,  be  remembered  that  rheumatism  is  a  very 
difficult  disease  in  which  to  estimate  the  value  of  curative 
measures,  and  the  real  truth  can  only  be  obtained  by  laborious 
investigation  and  the  most  open  statement  of  all  facts.  It  is 
not  to  be  supposed  that  the  pain  of  the  rheumatic  lesions  will 
be  speedily  quelled  by  this  method,  and  this  will  in  many  cases 
involve  the  employment  of  the  salicylates  which  must  greatly 
embarrass  the  case  when  viewed  by  the  believers  in  the  specific 
action  of  these  drugs. 

Our  experience  has  been  so  far  very  unconvincing  but  we 
have  learnt  this  practical  point,  that  if  these  vaccines  are 
potent  for  good,  they  need  to  be  used  very  cautiously  where 
there  are  active  cardiac  lesions,  and  we  would  warn  against 


432  TREATMENT 

the  wild  use  of  large  doses  simply  because  these  methods  are  so 
much  in  vogue.  We  ourselves  commence  with  the  dose  of 
1,000,000  and  find  our  way  cautiously  forward. 

The  serum  treatment  presents  also  great  difficulties  connected 
with  the  rapid  loss  of  virulence  of  the  micrococcus,  and  has 
been  unsatisfactory.  Yet  it  would  be  very  unwise  to  express 
formed  opinions  upon  either  method,  which  are  in  their  infancy 
and  which  may  in  the  future  vastly  improve  with  increasing 
knowledge. 


THE  PREVENTION  OF  ACUTE  RHEUMATISM 

The  possibility  of  doing  more  for  the  prevention  of  this  disease 
than  has  been  accomplished  heretofore  has  been  the  main 
purpose  of  our  investigations. 

We  believe  it  to  be  one  of  the  great  undertakings  in  the 
medical  history  of  this  country. 

The  importance  of  the  prevention  of  an  infection  which  is 
the  great  cause  of  organic  heart  affections  in  the  young  is  one 
that  cannot  be  over-rated  ;  and  we  believe  that  definite  results 
will  be  forthcoming  because  acute  rheumatism  is  met  with 
much  more  frequently  among  the  poorer  classes  and  is  encour- 
aged by  those  agencies,  which  may  be  summed  up  in  the 
single  word  "  poverty." 

We  are  now,  we  believe,  in  a  position  to  study  the  prevention 
of  this  disease  guided  by  a  definite  and  reasonable  working 
hypothesis,  and  one  which  though  it  exposes  our  limitations  is 
in  the  main  an  encouraging  brie. 

The  changeable  climate  and  seasons  of  this  country  are 
elements  beyond  our  control,  and  must  be  taken  into  account 
in  the  problem  of  prevention  as  baffling  influences.  Neverthe- 
less, that  these  agencies  are  not  wholly  responsible  for  the 
frequency  of  the  disease  is  clear  from  its  greater  incidence  upon 
the  poorer  classes. 

In  the  great  hospitals  it  is  clear  that  we  possess  ample  means 
for  treating  the  acute  disease  and  its  complications  and  for 
advancing  its  study  in  many  directions.  Their  value  might 
well  be  strengthened  in  the  future  by  the  establishment  of  some 
special  convalescent  homes  in  carefully  chosen  sites  for  those 
recovering  from  early  rheumatism  including  heart  disease  and 
chorea.  In  our  experience  the  ordinary  convalescent  home  is 
not  suited  for  such  cases,  particularly  when  they  are  children, 
for  they  need  constant  medical  supervision  and  nursing. 

We  are  convinced  that  the  medical  inspection  of  children  in 
the  State  schools  will  in  the  near  future  provide  us  with 
valuable   information   upon   the   influence   of   school-life   on 

433  28 


434  THE  PREVENTION  OF  ACUTE  RHEUMATISM 

chronic  rheumatic  heart  disease  and  on  the  relation  of  out- 
breaks of  acute  rheumatism  to  epidemics  of  sore  throats.  It 
ma}-  perhaps  be  hardly  realised  how  great  a  loss  of  time  and 
educational  energy  is  due  to  chorea  :  many  children  as  the  result 
of  this  illness  may  lose  as  much  as  three  months'  education 
each  year  for  some  years  in  succession.  It  is  possible  that 
careful  inquiry  may  discover  that  there  is  some  factor  in  our 
present  methods  of  education  which  introduce  too  great  a  strain 
or  perhaps  throw  a  peculiar  strain  upon  the  developing  brain 
of  these  children.  In  support  of  the  importance  of  the  medical 
inspection  of  school  children,  we  would  quote  from  the  annual 
report  for  1911,  of  the  Chief  Medical  Officer  of  the  Board  of 
Education,  Sir  George  Newman,  the  following  sentence  : 
"  School  inspection  provides  a  wide  field  for  inquiry  and 
research,  and  many  opportunities  of  bringing  home  the  danger 
of  neglecting  evidences  of  rheumatism  however  slight  in 
degree."  This  sentence  expresses  concisely  the  important, 
indeed  indispensable,  assistance  that  can  be  given  by  the  school 
medical  officers. 

The  education  of  parents  and  school-teachers  in  the  principal 
dangers  of  acute  rheumatism  might  well  be  carried  on  by  means 
of  simple  instructions  and  lectures.  Among  such  instructions 
may  be  suggested  the  following  for  rheumatic  children. 

1.  The  importance  of  proper  clothing. 

2.  The  care  of  sore  throats. 

3.  The  necessity  for  attention  to  "  growing-pains." 

4.  The  importance  of  undue  nervousness,  clumsiness,  and 
night-terrors  as  warnings  of  chorea. 

5.  Parents  should  be  warned  that  the  early  signs  of  heart 
disease  are  few,  and  that  shortness  of  breath  is  more  often 
complained  of  than  pain. 

6.  Much  emphasis  should  be  laid  upon  need  for  patience 
when  a  child  is  recovering  from  heart  disease. 

7.  Parents  should  be  told  that  rheumatism  is  very  liable  to 
recur. 

We  believe  that  more  attention  might  be  given  to  the 
condition  of  the  tonsils  and  naso-pharynx  in  the  rheumatic 
child,  and  also  to  the  choice  of  an  employment  for  those  who 
have  been  damaged  by  the  disease. 

The  view  that  acute  rheumatism  is  an*infective  disease  raises 


THE  PREVENTION  OF  ACUTE  RHEUMATISM  435 

again  the  important  questions  of  climatic  and  local  surround- 
ings, sanitation  and  conditions  of  housing.  The  possible 
relation  that  it  may  bear  to  other  infective  processes  such 
as  scarlet  fever,  measles,  diphtheria,  influenza,  or  even 
tuberculosis  seems  worthy  of  further  inquiry,  more  par- 
ticularly as  in  some  of  these  diseases  a  sore  throat  is  a 
prominent  symptom.  Investigations  in  these  directions 
would,  we  believe,  give  further  assistance  in  dealing  with 
the  problem  of  prevention,  and  come  into  the  province  of 
the  Medical  Officers  of  Health. 

We  are  convinced  that  the  general  subject  of  "  Rheumatism  " 
has  only  reached  the  threshold  of  inquiry,  and  that  in  every 
direction  new  fields  for  research  and  inquiry  are  before  us. 

In  conclusion,  this  is  certain ;  that  at  the  present  time,  in  spite 
of  all  that  has  been  written  upon  the  treatment  of  acute  rheu- 
matism, there  are  hundreds  of  young  children  who  are  so 
damaged  by  this  disease  that  all  known  methods  of  "  cure  " 
are  utterly  useless  to  them.  It  is  to  prevention,  then,  that  we 
look  for  some  advance  from  this  grievous  state  of  affairs,  and 
it  is  with  the  desire  of  directing  the  attention  of  our  profession 
to  this  pressing  need  that  we  have  ventured  to  publish  this 
book,  in  the  hope  that  it  may  have  some  influence  toward 
achieving  this  end. 


INDEX 


Abdominal  pains,  obscure  in  acute 
rheumatism,  361 
symptoms  in  acute  rheumatism, 
422 
Abrahams,    Bertram,    pathology    of 

rheumatic  chorea,  174 
Acetic    acid,    production    by    diplo- 

bacillus,  217 
Achalme,  bacillus  of,  alleged  trans- 
formation of  diplococcus  into, 
266 
bacteriology   of    acute   rheuma- 
tism, 96,  97,  109 
Adrian,  experimental  production  of 

appendicitis,  372,  373 
Adult,  acute  rheumatism  in,  411 

active    rheumatism    in    causing 

injury  to  heart  muscle,  51 
chronic  rheumatic  heart  disease 

in,  59 
prognosis  of  acute  rheumatism 
in,  426 
Akerman,    experimental    osteo-mye- 

litis,  363,  364 
Alcoholism,  adverse  effect  on  dilata- 
tion  of    heart    of    rheumatic 
origin,  416 
extreme   changes    in    left    ven- 
tricle from  case  of,  48,  51 
Alimentary  canal,  lesions  of  in  acute 
rheumatism,  407,  408 
saprophytic  streptococci  of,  270 
Anaemia,       rheumatic,       malignant, 

process  favoured  by,  355 
Andrews,  H.  Russell,    and  Wall,  C. , 
chorea  occurring  in  pregnancy,  260 
Angina  from  throat  affections,  resem- 
blance of  venous  thrombosis  in 
neck  to,  77 
faucium,     experimental     results 

from  case  of,  107,  132 
relation  to  acute  rheumatism,  96 
rheumatic,  406 
Aorta,   acute    inflammation,   termi- 
nating in  sudden  death,  67 
Aortic  and  mitral  disease   of  rheu- 
matic origin,  317-321 


Aortic    and  mitral    disease,    clinical 
study  of,  319 
regurgitation  in  childhood,  415 
valves,    condition   in   rheumatic 
heart  disease,  34,  39 
Apathy,  mental  in  rheumatic  venous 

thrombosis,  77,  78 
Apert,     bacteriology     of     rheumatic 
fever,  97 
diplococcus  in  rheumatic  chorea, 

234 

pathology  of  rheumatic  chorea, 

175 
Appendicitis,  aetiology  of,  374-377 

bacteriology  of,  difficulties  in, 
379.  380 

blood-infectionincausation|of,382 

experimental,  produced  by  diplo- 
coccus from  acute  rheumatism, 
367-73,  408,  422 

morbid  anatomy  in  human  and 
experimental  disease,  com- 
parative study  of,  378-83 

point  of  origin  in  human  subject, 

373 
relapsing,  382 

relation  of  rheumatism  to,  377 
resulting    from    blood    infection 

from    streptococcal    follicular 

tonsillitis,  374-377 
rheumatic,  3 

question  of,  381 
secondary  causes  of,  382 
streptococcus  as  cause  of,  380 
tonsillitis  in  relation  to,  379 

See  also  Perityphlitis 
Appendix      vermiformis,     lymphoid 

tissue  in,  360 
solitary   ulcer    in,    produced   in 

rabbits    by    intravenous    in- 
jection of  diplococcus,  383 
and  tonsils,  structural  analogy, 

359,  360 
Arrhythmia  (cardiac),  268 
Arteritis  in  rheumatic  infection,  404 
Arthritis    affecting    one    joint.     See 

Monarthritis 


437 


438 


INDEX 


Arthritis,  and  fatal  endocarditis  pro- 
duced in  rabbits  from  inocula- 
tion of  strepto-diplococci  from 
enucleated  tonsil,  274 

and  purulent  pericarditis  fol- 
lowing mixed  infection  by 
staphylococcus  aureus  and 
diplococcus,  223 

associated  with  perityphlitis, 
pyaemic  nature  of,  364,  365 

certain  forms  of,  150-161 

cervical,  413 

simulating   spinal   caries, 

413 

chronic,     infectivity     of     acute 

rheumatism  in  relation  to,  136 

diagnosis  assisted  by  recognition 

of  rheumatic  dilatation,  26,  27 

effusions  about  joints  in,  142 

sterility,  144 
experimental,      effusion      about 
joints  in,  142,  143 
sterility,   144 
experimental,  produced  by  intra- 
venous inoculation  of  dip- 
lococcus    isolated     from 
cases  of  rheumatic  fever, 
141-44,  154,  155 
production,  in  rabbits,  6 
gelatinous    swelling    of    fibrous 
structures  in  last  stages  of,  144 
gouty,  399 

implication  of  bursaein,  413 
in    association    with    perityph- 
litis, 359-66 
in  acute  rheumatism  in  children 
under  five  years,  283,  286-98 
in  scarlatinal  rheumatism,  treat- 
ment, 300 
infantile,  153-4 

suppurative,  cause  of,   case 
described,  159 
investigations  upon,  275 
malignant  and  rheumatoid,  207 
multiple,  in  rabbit  from  inocu- 
lation with  diplococcus  from 
case  of  osteo-arthritis,  147,  149 
non-suppurative,  2,  3 
pneumococcus,  157 
production    by   intravenous   in- 
jection   of    diplococcus    rheu- 
maticus,  275 
rheumatic,  acute,  398,  399 

condition      of      connective 
tissues  of  synovial  mem- 
branes in,  399 
condition  of  tendon  sheaths 
in,  399 


Arthritis,  rheumatic,  course  of,  413 
of  morbid  processes  in, 
152 
escape    of    micro-organisms 
into    joint    cavity,    vital 
process,  152 
every  variety  found,  398 
experimental       production, 

151.  152 
local       periostitis,       round 

affected  joints  in,  399 
malignant,  399 
most  easily  overcome  of  all 

rheumatic  lesions,  230 
osteo -arthritic     type,     ex- 
perimental      production, 
145-149 
See  also  Osteo-arthritis 
periostitis  with,  414 
perivascular  fibrosis  in,  153 
resembling  perityphlitis,  365 
rheumatoid,  2,  3,  151,  154-7 

and  rheumatic  fever,  156-7 
bacteriology  of,  148 
case    with    features    resem- 
bling, 289 
cases  of  rheumatic  arthritis 
passing  into  condition  of, 
398 
infection,  results  of  experi- 
mental inoculations,  155 
infective,    causation,     sum- 
marised, 161 
nervous  lesions,  155 

puerperal  origin,  155 
serum  for,  Menzer's,  161 
treatment,  summarised,  161 
want    of    exact    knowledge 
concerning  leads  to  errors 
in     diagnosis     of     rheu- 
matism, 425 
suppurative,  157-160 

difficultiesof  terminology,  157 
from   gonococcus  infection, 

case  described,  160 
from  streptococcus  pyaemia, 

case  described,  160 
rheumatic  origin  proved,  by 
isolation    of    diplococcus, 
case,   158 
various  forms  mistaken  for  rheu- 
matism, 425 
Aschoff  and  Tawara,  gross  changes  in 

cardiac  muscular  fibres,  268 
Ashby,    H.,    on   scarlatinal   rheuma- 
tism, 302 
Auriculo-ventricular  bundle,  damage 
to,  in  lesions  of  myocardium,  404 


INDEX 


439 


Bacillus   as  causal  agent  in  acute 

rheumatism,  theory  as  to,  ioo 

of  Achalme,  96,  97,  109,  no 

coli  in  perityphlitis,  364 

pyogenes,  fcetidus  liquefaciens,95 

Bacteria,  antitoxic  sera  set  free  from, 

producing  effusion  into  joints,  230 

Bacterial   cause   of   specific    disease, 

demonstration  of,  228 
Bacteriology, advances  in,  results  of,  4 
of  acute  rheumatism,  history  of, 

94-101 
of    appendicitis,    difficulties    in, 

379,380 
of  rheumatoid  arthritis,  148 
Bannatyne,  rheumatoid  arthritis  as  a 
specific  disease,  154 
Wohlmann,    and    Blaxall,    bac- 
teriology of  rheumatoid  arth- 
ritis, 148 
Barlow,  Sir  T.,  affections  of  heart  ir. 
rheumatic  children,  181 
association  of  chorea  and  rheu- 
matic fever,  177 
development  of  chorea,  270 
on  scarlatinal  rheumatism,  302 
and    Warner,    F.,    identity   be- 
tween rheumatic  process  and 
rheumatic  nodule,  80 
Barnard,  H.,  and  Hill,  L.,  function 
of  pericardium  in  relation  to  heart 
wall,  66 
Bastian,  H.  C.  pathology  of  rheumatic 

chorea,  173 
Beaton  and  Ainley  Walker,  isolation 
of  diplococcus  from  case  of  rheu- 
matic chorea,  235 
Beattie,  experimental  production  of 

twitching  movements,  239 
Bile   from   infected     rabbits,    diplo- 
coccus isolated  from,  422 
Blaxall,  bacteriology  of  rheumatoid 
arthritis,  148 
rheumatoid  arthritis  as  a  specific 
disease,  154 
Blood  changes  in  acute  rheumatism, 
66,  421 
cultures,    as   evidence   of   rheu- 
matic   origin    of    simple    and 
malignant    endocarditis,    dis- 
puted value  of,  327 
infection  from  streptococcal  fol- 
licular    tonsillitis     producing 
appendicitis,  374-77 
in  causation  of  rheumatism  ,382 
staphylococcus  pyogenes  aureus 
found  in,   in  mixed  infection 
with  diplococcus,  222 


Brain,  blood-vessels,  engorgement,  in 
cases  of  chorea,  246,  249,  251, 

253 
diplococci    found    in,    in     fatal 
cases  of  chorea,  248,  250, 
252 
in  acute  rheumatism,  405 
in  chorea,  170,  238 
hyperaemia  in   cases   of   chorea, 

246,  249,  251,  253 
pathological  changes  in,  in  acute 

rheumatism,  405 
perivascular   round-cell  infiltra- 
tion in,  in  cases  of  chorea,  246, 
249,  251,  253 
and  membranes,  occurrence  in,  of 
diplococcus    found    in    acute 
rheumatism,  128 
Brazil,    perityphlitis    with    arthritis, 

362 
Bright's     disease,     resemblance     of 
venous    thrombosis     in     neck    to, 

77 

Broadbent,  Sir  W.,  origin  of  rheu- 
matic chorea,  172. 

Broncho-pneumonia,  rheumatic,  3, 
407,  419 

Buist's  statistics  of  chorea  in  preg- 
nancy, 260 

Bullous  eruptions  rare  in  acute 
rheumatism,  421 

Bursa?,  implication  in  arthritis,  413 

Bursitis,  142 

Buss,  relation  of  angina  faucium  to 
rheumatic  fever,  96 

Butterfield,  H.  G.,  research  on  endo- 
carditis, 324 


Caiger,   F.  F.,   on  scarlatinal  rheu- 
matism, 301 
Cardiac  dullness,  area  in  children,  14 
grouped  according  to  severity 
of  heart  affections,  15-27 
impulse,  position  in  younger  and 
older  children,  15 
Carditis,   acute,   with  fatty  changes 
throughout  heart-wall,  52 
rheumatic,  2,  49 

acute,  pulmonary  oedema  in, 

407,  420 
experimental       production, 

268 
gross  changes  in   muscular 
fibres  of  heart  in,  267,  268 
myocardial  lesions  in,  403, 

404 
pleurisy  in,  406 


440 


INDEX 


Carditis,    scattered    foci    of    inflam- 
matory   change    in    con- 
nective tissue  framework 
of  heart  in,  267 
severe,        with       extensive 
venous  thrombosis, 
cases  of,  68-78 
clinical   history,    68, 

7°.  72 
post  mortem  results, 

69,  71.  73,  74 
Cave,  pneumococcus  arthritis,  157 
Charrin,  bacteriology  of  acute  rheu- 
matism, 95 
Chauffard  and  Raymond,  diplo-bacilli 

in  rheumatoid  arthritis,  154 
Cheadle,  W.   B.,  angina  faucium  in 
relation  to  rheumatic  state  in 
childhood,  96 
case  of  rheumatic  heart  disease 

with  fibrosis  of  ventricle,  52 
chorea  in  rheumatic  children,  178 
concurrent  myo-  and  pericardial 

changes,   49 
development  of  chorea,  270 
fatal  acute  rheumatism,  detailed 

case,  167 
pathology  of  rheumatic  chorea, 

174 
rheumatic    venous    thrombosis, 

77.78 
Chemical    theories    of    causation    of 

rheumatism,  388,  394 
Childhood,    aortic    regurgitation    in, 

415 

rheumatic  heart  disease  in, 
clinical  evidences  slender,  415, 
416 

sex    incidence    of    acute    rheu- 
matism greater  among  females 
in,  390 
Children,  acute  rheumatism  in,  9 
fatality  of,  59 
prognosis,  426 

area  of  cardiac  dullness  in,  14 

association  of  chorea  and  rheu- 
matism in,  177,  178 

chorea  in,  with  acute  dilatation 
of  heart,  13-43 

measles  and  diphtheria  in,  fol- 
lowed by  acute  rheumatism, 
301 

muscular  pains  in  acute  rheu- 
matism in,  144 

of  London,  prevalence  of  acute 
rheumatism  among,  393 

rheumatic,  enucleation  of  en- 
larged tonsils  in,  273,  274 


Children,  rheumatic,  enlarged  tonsils 
in,  hygienic  care  of,  434, 

435 
nervous  and  emotional,  259 

rheumatic  fever  of,  affections  of 
heart  in,  181,  182 

rheumatism  in,  acute  dilatation 
of  heart  in,  13-43 

scarlatinal  rheumatism  in,  fol- 
lowed by  heart  disease,  302 

under  five  years,  rheumatism  in, 
281-98 

with  slight  surgical  ailments, 
condition  of  heart  in,  28-31 

younger  and   older,   position  of 
cardiac  impulse  in,  15 
Chorea,  action  of  bacterial  toxins  on 
the  nerve  cells  in,  255,  256 

and  acute  rheumatism,  experi- 
mental effects  of  diplococcus 
from  fatal  case,  218 

association  with  acute  rheuma- 
tism, frequency  of,  257 

changes  in  heart  wall  in  fatal  case 
of,  58 

chromatolysis  of  nerve-cells  in, 

254 
chronic   forms,   area   of  cardiac 

dullness  in,  23 
comparison    with    acute    rheu- 
matism, 258 
connection  of  acute  rheumatism 

with,  98 
development  with  subcutaneous 

nodules,   414 
diagnosis  by  means  of  medical  in- 
spection of  school  children,  434 
diplococcus  in  brain,  in  case  of, 

238 
explanation  of,  2 
fatal  pericarditis  with,  238 
first  attack,  -with  acute  dilatation 

of  heart  followed  by  valvulitis, 

area  of  cardiac  dullness  in,  20 
first  attacks  without  history  of 

rheumatism,    area   of   cardiac 

dullness  in,  17 
first  and  last  symptom  of  acute 

rheumatism,  257 
Huntington's,  pathological 

changes  in,  177 
in  children,  acute  dilatation  of 

heart  in,  13-43 
in  fatal  cases  of  rheumatic  heart 

disease,  34,  41 
in  rheumatism  in  children  under 

five    years,    283,    286-8,    290, 

291-4,  297,  298 


INDEX 


441 


Chorea,    local     lesions    of      nervous 
system,  as  cause  of,   237,  238, 

239 
movements    in,   ^etiological  fac- 
tors, 253,  254 
occurring  in  pregnancy,   patho- 
logy  similar  to   infantile 
form,  260 
probably  rheumatic,  259 
with    previous    history    of 
chorea  or  rheumatism,26o 
fatal  case,  244,  250 

bacteriological     exami- 
nation,   252 
clinical  history,  250 
diplococcus    found    in, 

252,  260 
endocarditis   found  in, 

250,  251,  260 
macroscopical  and  mi- 
croscopical examina- 
tion, 251 
overstrain  of  nervous  system  in 

relation  to,  259 
pathology  of,  244,  252-9 
predominant  affection  of  motor 

system  in,  256 
premonitory  stage,  270 
relapses  of,  258 
rheumatic,  234,  417,  418,  427 
active  rheumatism,  cause  of 

death  in,  57 
association    of    diplococcus 
with,  234,  235 
with  mitral  stenosis,  390 
clinical    characteristics     of, 

176 
decrease  after  puberty,  418 
experimental  production,  in 

rabbit,  134,  235 
fatal    cases,    bacteriological 
examination       post- 
mortem, 248,  250 
clinical  history,  245,248 
macroscopical     exami- 
nation post  mortem, 
246,  249 
microscopical  examina- 
tion       post-mortem, 
249 
fright  as  factor  of,  177,  259 
in  children,  177,  178 
in  fatal  case  of  acute  rheu- 
matism, 235,  236 
isolation  of  diplococcus 
post-mortem,  236 
metastatic  nature  of,  258 
pathology  of,  169-176 


Chorea,      rheumatic,     toxic     origin, 

theory  as  to,  237 

severe,  with  early  endocarditis, 

specimen  of  mitral  valve  from, 

238 

treatment  by  rest  indicated  by 

cardiac  dilatation,  27 
vascular  changes  in  brain  in,  246, 
249,  251,  253 
Chromatolysis      of      nerve-cells      in 

chorea,  254 
Church,   Sir  W.,  insidious   onset  of 

acute  rheumatism,  207 
Chvostek,   micro-organism    in    urine 

from  cases  of  rheumatic  fever,  95 
Climate,  in  relation  to  prevalence  of 

rheumatism,  392 
Cole,    Rufus,    experimental    produc- 
tion of  arthritis  and  endocar- 
ditis, 231 
experimental      production       of 
twitching  movements,  238 
Colitis,  mucous,  between  attacks  of 
acute  rheumatism,  422 
in  acute  rheumatism,  408 
Coombs,    Carey,    gross    changes    in 
cardiac  muscular  fibres,  268 
on  submiliary  nodules,  396 
Coyon,     bacteriology    of    rheumatic 

fever,  97 
Cullen,     astiology     of     acute     rheu- 
matism, 387 

Dana,    bacteriology   of   acute   rheu- 
matism, 95 
diplococcus  in   rheumatic  chorea, 

234 
pathology   of    rheumatic    chorea, 

174.  175 
Death,    sudden,   frequency  in   rheu- 
matic heart  disease,  34,  41 
in  fatty  degeneration  of  heart,  51 
terminating    acute     inflammation 
of  aorta,  67 
Dental  cases  in  acute  rheumatism  ,408 
Diarrhoea  in  acute  rheumatism,  422 
Dickinson,    W.    H.,    origin   of   rheu- 
matic chorea,  172 
Diet  in   acute  rheumatism,    general 
rules  for,  431 
possesses    no    influence    on    inci- 
dence    of     acute    rheumatism, 

394 
Diphtheria  and  rheumatism,   effects 
of  dilatation  of  heart  in,  com- 
pared, 60 
changes    in    heart-wall    in     fatal 
case,  54-56 


442 


INDEX 


Diphtheria,   changes   in   heart    wall 
similar    to     those     in     acute 
rheumatism,  89 
in  children,   acute    rheumatism 
following,  301 
Diplobacillus,    production    of    acetic 
acid  by,  217 
of  formic  acid  by,  217 
Diplococci   in   brain  in   acute   rheu- 
matism, 405 
in     vegetations     of     malignant 
rheumatic  endocarditis,  403 
Diplococcic  infection  of    acute  rheu- 
matism   through    placental   circu- 
lation, 389 
Diplococcus       and       staphylococcus 
aureus,  effect  of  simultaneous 
injection  on  monkeys,  222 
as  causal  agent  of  acute  rheuma- 
tism, 6,  165-183,  388,  389 
demonstration     by     experi- 
ments on  rabbits,  103-7, 
111-120 
demonstration    from    cases, 

109,  no,  115-120 
theory  as  to,  100,  102-7 
See  also  under  Diplococcus 
rheumaticus  (below) 
association       with       rheumatic 

chorea,  234,  235 
at  siteof  local  lesionsinacuterheu- 
matism  rapidly  destroyed,  135 
constancy  of  appearance  in  acute 

rheumatism,  263,  264 
difficulty  of  detection  in  human 
tissues,  134 
in  valves  of  heart,  134 
exciting    cause    of    acute    rheu- 
matism, 263 
found     in     acute     rheumatism, 

95-97 
demonstration     in     tissues, 

124. 134 
identity     with      diplococci 
previously  observed,   122 
inoculation    causing    endo- 
carditis, 215 
long  persistence  in  body,  208 
occurrence     in     brain     and 
membranes,  128 
in  heart,  124 
in  joints,  126 
in  kidney,  125,  126 
in  liver,  126 
in  lungs  and  pleurae, 

127 
in  nodule,  125 
in  throat,  128 


Diplococcus,    points    of    distinction 

from       staphylococcus 

pyogenes    aureus,    218, 

219,  222 

question  whether  specific 

organism,  123 
found    in    fatal   case     of 
chorea      occurring     in 
pregnancy,  252,  260 
found    in    joints   in    mixed    in- 
fection   with    staphylococcus, 
222 
from   case  of  fatal  chorea   and 
rheumatic  fever  experi- 
mental effects,  218,  219 
of  rheumatic  fever  inocu- 
lated intravenously  into 
rabbit  producing  acute 
iritis,  213-214 
of    rheumatic  meningitis, 
inoculation  into  rabbits, 
results,  241,  242 
from  tonsils,  in  rheumatic  fever, 

180 
in  brain,  associated  with  begin- 
ning of  rheumatic  cho- 
rea, 170 
in  case  of  chorea,  238 
in     polymorphonuclear     leuco- 
cytes,   178 
in  rheumatic  nodule,  83    n. 
in  scarlatinal  rheumatism,  portal 

of  entry,  300 
intravenous  injection  into   rab- 
bits producing  solitary 
ulcer  in  appendix,  383 
inoculation  into  monkeys, 
results,  220,  221 
into  rabbits,  effects, 
103-7,    111-115, 
117-20,  220 
isolated    from    case    of    osteo- 
arthritis.inoculated  into 
rabbits,     results,     148, 

150 

from  cases  of  rheumatic 
fever,  intravenous  ino- 
culation, causing  arth- 
ritis, 141-44,  154.  J55 

in    rheumatoid    arthritis, 

155 
post-mortem  from  case  of 

acute  rheumatism  with 

chorea,  236 
from    case   of   rheumatic 

arthritis,  151 
from  cases  of  rheumatic 

pericarditis,  264,  265 


INDEX 


443 


Diplococcus  isolated  from  urine 
during  attack  of  acute  peri- 
carditis, 135 

local  injection,   producing   peri- 
carditis, 258 

metamorphosis  of,  alleged,  266 

morphology  of,  121 

proof    of  .rheumatic    origin    of 
arthritis,  case,  158 

rheumaticus,  154 

cause  of  rheumatic  fever, 

227,  228 

causing  experimental  ap- 
pendicitis, 408 
chief  characteristics,  395 
choice  of  term  defended, 

228,  229 

clotting  of  milk  by,  233 
culture,  method  of,  326 
demonstration     in    cases 
of    acute   rheuma- 
tism, ante-mortem 
and    post-mortem, 
229 
fulfilling  Koch's  pos- 
tulates,   228,    229, 
232 
discovery  difficult,  230 
in  cases  of  sero-fibri- 
nous     pericarditis 
and  rheumatic 

endocarditis,    231 
from   acute  lesion,  intra- 
venous inoculation  into 
rabbit    producing    ap- 
pendicitis, 367-73 
inoculation    causing    ap- 
pendicitis, 422 
intravenous  injection  pro- 
ducing arthritis,  275 
inoculation  of  chorea 
produced     by,     in 
rabbit,  176 
isolation     from     bile     in 

infected  rabbits,  422 
isolation    of,    matter    of 
routine,  in  both  simple 
and    malignant    endo- 
carditis, 324 
and   of   malignant   endo- 
carditis, identical,   190 
investigated       cases, 
189-199 
peculiarities  of,  233 
resistance    of   rabbits   to 

inoculation  by,  233 
sites  where  found  in  body, 
230,  231 


Diplococcus,  specific  test  for,  needed, 
232 
submiliary    nodules    pre- 
sent    in     experimental 
lesions  produced  by,  397 
virulence  difficult  to  raise, 

233 
where    most    easily    ob- 
tained, 402 
staining  of,  122 

See  also  Staphylococcus  pyo- 
genes    aureus    and     diplo- 
coccus, mixed  infection 
Dropsy,  in  rheumatic  heart  disease, 
condition  of   heart   as   found 
post-mortem,  40 
frequency,  34,  40 
Duckworth,     Sir    Dyce,    chorea    in 
children,  178 
development  of  chorea,  270 
pathology  of  rheumatic  chorea, 

174 

von  Dungern  and  Schneider,  bac- 
teriology of  rheumatoid  arthritis, 
148 

Dunlop,  Dr.  G.  H.  M.,  development 
of  rheumatism,  270 

Dysmenorrhoea  in  acute  rheumatism, 
423 

ELECTRO-cardiography,  use  of,  404 
Empyema  in  pneumococcal  pericar- 
ditis, 285 
Endocarditis,    absence    in    pneumo- 
coccic  pericarditis,  285 
early,  with  severe  chorea,  speci- 
men of  mitral  valve  from,  238 
experimental,  production  by  ino- 
culation of  diplococcus  from 
acute  rheumatism,  215 
fatal,  and  arthritis,  produced  in 
rabbits    from    inoculation    of 
strepto-diplococci    from    enu- 
cleated tonsil,  274 
following  rheumatic  fever,  156 
identity    of    rheumatic    nodule 
when  stained  with  appearances 
in,  81 
infective,  fatal  case  with  acute 
inflammation   of     ven- 
tricle-wall, 52 
relation    to    acute    rheu- 
matism, 88 
malignant,      and      simple,      of 
possible  rheumatic  ori- 
gin, 312 
associated      with      rheu- 
matic fever,  1 85-1 91 


444 


INDEX 


Endocarditis,     malignant,     chronic, 
swellings  at  finger-ends  in 

(Osier's  sign),  414 
due  to  acute  rheumatism, 

228,  270 
onset,  insidious,  207 
or    infective     term     dis- 
cussed, 186 
streptococcus         causing 
acute  rheumatism  also 
cause  of,  270 
present  in  fatal  case  of  chorea 
occurring  in  pregnancy,   250, 
251,  260 
produced  by  streptococcus,  267 
rheumatic,  4 

acute,  415 

associated  with  peri- 
carditis, 415 
nephritis  in,  421 
discovery   of   diplococcus 
in      malignant      cases, 
231 
identity      of      rheumatic 
nodule  with  process  in, 
80 
malignant,  138,  188,  268, 
269 
almost        invariably 

fatal,  354 
bacteriology,   203-5 
details     of     investi- 
gated  cases,    189- 
201 
diplococci    in     vege- 

tions,  403 
existent  before  symp- 
toms    are     mani- 
fested, 269 
fatality  great,  427 
favoured  by  anaemia, 

356 
histology,  201-3 
prophylaxis,  355 
treatment,  355 
relation  of  infective  endo- 
carditis to,  129,  130 
simple,  402 
streptococcus,        isolated 

from  case  of,  98 
with  fibrosis,  403 
simple     and     malignant,     rheu- 
matic,   blood    cultures 
as  test,  disputed  value 
of,  327-9 
evidence  from  100  mitral 
and  aortic  cases,  329- 
356 


Endocarditis,  simple  and  malignant, 
fibrous  tissue  surround- 
ing,   micrococci    latent 
in,  325 
histology,  323-7 
proof  of  theory,  321 
unsatisfactory  terminology,  333, 
356 
Endocardium,  clinical  importance  in 
heart  disease,  63 
inflamed,  post-mortem    appear- 
ance    in     severe     rheumatic 
fever,  64 
Epistaxis,  in  acute  rheumatism,  419 
Erythema  in  acute  rheumatism,  420 
Erythemata,    in    rheumatic    venous 

thrombosis,  78 
Extremities,  upper,  and  neck,  throm- 
bosis of  large  veins  of  cause  of  death 
in  rheumatic  pericarditis,  48 

Fasci*,  affected    in  acute  rheuma- 
tism, 400 
Female,    adult,    stenosis    of    mitral 
valve    of     rheumatic      origin    in, 
412 
Females,  sex-incidence  of  acute  rheu- 
matism  greater  among,   in  child- 
hood, 390 
Fever  in  acute  rheumatism,  422,  423 
See  also  Hyperpyrexia  (Rheu- 
matic) 
in  rheumatic  fever,  as  primary 

symptom,  investigations,  180 
in     rheumatic     venous     throm- 
bosis, 78 
Fibrosis,  perivascular,  in  rheumatic 

arthritis,  153 
Fibrositis,  413,  414 

as  form  of  lumbago,  413 
rheumatic,  400,  401 
Finger-ends,  swellings  at,  in  chronic 
malignant     endocarditis      (Osier's 
sign),  414 
Fisher,   T.,   pathological  changes  in 
myocardium    apart   from   pericar- 
ditis, 49 
Forbes,   Graham,   strepto-diplococci, 
recovered  from  depths  of  diseased 
tonsil  by,  275 
Formic  acid,  intravenous  injections, 
experimental,  237 
production  by  diplobacillus,  217 
and  streptococci,  233 
Forster,    F.    C,    case    of    rheumatic 

iritis,  210 
Fowler,    Sir    J.    K.,    tonsillitis    pre- 
ceding acute  rheumatism,  96 


INDEX 


445 


Fraenkel,       submiliary       rheumatic 

nodules,  405 
French,  H.  S.,  and  Hicks,  H.  T.,  cases 

of  chorea  gravidarum,  260 
Fright,  in  relation  to  chorea,  259 
Fritz  Meyer,  rheumatic  arthritis,  151 
Froriep,  rheumatic  fibrositis,  400 

Gandy     and     Borgnait     Legneule, 
microscopical    changes    in     rheu- 
matic hyperpyrexia,  242 
Garrod,  Sir  A.  B.,  chemical  theory  of 
causation  of  acute  rheumatism,  388 
Garrod,  A.  E.,  F.R.S.,  fever  in  rheu- 
matic fever  as  primary  factor, 
doubtful,  180 
incubation  of  rheumatic  fever, 

179 
post-mortem  findings  in  chronic 
rheumatic    heart    disease    in 
adults,  60 
rheumatic    venous    thrombosis. 

77,  78 
Gatay,  rheumatic  phlebitis,  76 

rheumatic  venous  thrombosis,  78 
Gingivitis  in  acute  rheumatism,  408 
Goadby,    K.   W.,   dental  caries  and 
gingivitis  in  acute  rheumatism,  408 
Gonorrhoea,  cause  of  multiple  arth- 
ritis, case  described,  160 
infection     from,     in     rheumatic 

iritis,  210,  211 
infective   process  in,    compared 
with  acute  rheumatism,  354 
Goodhart,  Sir  J.  F.,  chorea  in  rheu- 
matic children,  178 
myocardial     disease     in     rheu- 
matism, 416 
Gordon,    Mervyn,    differentiation   of 
streptococci,  233 
streptococcus       isolated      from 
scarlet  fever  by,  299,  302 
Gout,  acute,  developing  in  adult  life 
in  subject  of  acute  rheumatism  in 
childhood,  390 
Gowers,  Sir  W.,  pathology  of  rheu- 
matic chorea,  174 
rheumatic  fibrositis,  400 
Grant,     Sir    J.,    perityphlitis    with 

arthritis,  362 
Guttmann,  aetiology  of  rheumatism, 
94.95 


Haig,  A.,  uric  acid  theory  of  cau- 
sation of  acute  rheumatism,  388 

Heart,  condition  of,  in  children  with 
slight  surgical  ailments,  28-31 


Heart,  condition  of,  in  healthy  public- 
school  boys,  31-33 
coronary   circulation  within,  ar- 
rangement, 64 
dilatation,  acute,  in  first  attack 
of  chorea  followed 
by  valvulitis,  area 
of  cardiac  dullness 
in,  20 
in    rheumatism    and 
chorea     of     child- 
hood, 13-43 
rheumatic,  death 

from,  rare,  416 
effects  in  diphtheria  and 
rheumatism  compared, 
60 
extreme  in  case  of  rheu- 
matic pericarditis, 
44-52 
co-existing     without 
severe        valvular 
disease,  49 
in      acute       rheumatism 
marked,         co-existing 
with      slight      clinical 
symptoms,  50,  51 
indication    against    para- 
centesis pericardii,  27 
indication  for  rest  in  treat- 
ment of  chorea,  27 
of  rheumatism,  27 
main  cause  of  increase  in 
area  of  dullness  in  rheu- 
matic pericarditis,  23 
pericarditis  as  cause  of,  66 
rheumatic,   adversely  in- 
fluenced by  alcoholism, 
416 
disease,  cardiac  dullness  in  chil- 
dren   grouped    accord- 
ing to  severity  of,  15-27 
clinical  evidences,  63 
following  scarlatinal  rheu- 
matism in  children,  302 
gravity  of  case  determined 
more  by  symptoms  than 
clinical  signs,  64 
in  acute  rheumatism,  181- 

183 

in   acute   rheumatism   of 
children      under      five 
years,  283,  286-98 
See  also  Heart  Disease 
rheumatic,  below 

production    by    infection 
from  inflamed  tonsil,  2 

rheumatic,  2 


44^ 


INDEX 


Heart  disease,  rheumatic,  acute 
changes  in  heart 
found  after  death, 
origin,  50 

acute,  severe  cases, 
with  definite  val- 
vulitis, area  of  car- 
diac dullness  in,  21 

with  pericarditis, 

area  of  cardiac 
dullness  in,  21 

age-incidence,  34,  35 

analysis  of  150  cases 
(Hospital  for  Sick 
Children,  Great 
Ormond  Street  and 
St.  Mary's  Hos- 
pital), 34-43 

association  of  sub- 
cutaneous nodules 
with,  414 

cellular  exudation  in 
foci  spreading 

through  heart  wall 
in,  65 

chorea  in  fatal  cases, 

34-  4i 
chronic,     failure     of 
compensation 
in,    with   his- 
tory of  relapse 
of        rheuma- 
tism, 64 
in  adults,  59 
combinationof  valvu- 
lar lesions  in,  34,  39 
condition     of     myo- 
cardium      in, 

34.  37 
pericardium    in, 

34.  36 
of  valves  in,  34, 
38,  39 
course  of,  413 
developing  in  infant 

in  utero,  389 
diagnosis  must  not  be 
delayed    till    mur- 
murs are  heard,  60 
dilatation  chief  cause 
of  fatal  issue, 

24.37 
frequency      and 
importance 
shown      post- 
mortem, 26 
prognostic     im- 
portance of,  27 


Heart    disease , 


rheumatic,  dilata- 
tion in,  recognition 
assists  in  diag- 
nosing arthritis, 
26,  27 

evidence  of  fresh 
rheumatic  mani- 
festations in  fatal 
cases,  34,  39 

factor  in  heart  failure 
of,  268 

fatal  first  attacks,  34, 

35 

fibrosis  of  left  ven- 
tricle in  case  of,  48 

foci    of    necrosis    in, 

4°3 
frequency  of  dropsy 
in,  34,  40 
of   nodules  in 
fatal    cases, 

34.4° 

gravity  of,  427 

importance  of  myo- 
cardium in,  8 

important  part 

played  by  active 
rheumatism  in,  59 

in  childhood,  clinical 
evidences,    slender 

415 

incurable,  produc- 
tion of,  60 

indicated  by  acute 
dilatation,  27 

microscopy  of,  44,  47 

myocardial  damage 
in,  416 

pericardial  friction 
in,  towards  end  of 
fatal  illness,  34,  40 

post-mortem  appear- 
ances in  fatal  cases, 

41-43 
progressive     chronic 

forms,  416 
relation     to     scarlet 

fever,  34,  35 
season  in  which  fatal 

attack  commenced, 

34.  35 

sex  incidence,  34 

sudden  death  in,  fre- 
quency, 34,  41 

treatment  by  sali- 
cylate of  soda,  27 

with  fibrosis  of  ven- 
tricle, 52 


INDEX 


447 


Heart,  fatty    degeneration   through- 
out, how  resulting,  165 
in     acute     cases     of    rheu- 
matism with  pericarditis, 
66 
fatty     degeneration     advanced, 

sudden  death  in,  51 
muscular  fibres  of,  gross  changes 
in,   in    rheumatic    car- 
ditis, 267,  268 
bacterial  origin,  268 
occurrence  of  diplococcus  found 

in  acute  rheumatism  in,  124 
power  of,  undermined  by  rheu- 
matic affection  of  pericardium, 
60 
scattered   foci   of   inflammatory 
change   in   framework   of,    in 
rheumatic  carditis,  267 
valves  of,  difficulty  of  detection 
of  diplococcus  in,  134 
granulations     in,     found 
post  mortem  in  cases  of 
chronic  disease  in  adults 
of  rheumatic  origin,  59 
when  possible  to  compen- 
sate lesion,  23 
See  also  Mitral  valve 
Heart  failure,   cases  ending  fatally, 
accompanied   by  fresh  mani- 
festations of  rheumatism,  23, 
39 
cause  of  death  in  case  of  acute 
virulent  rheumatism  with  ex- 
tensive purpura,  86,  87 
Heart -muscle,  alterations  other  than 
fatty  in  acute  rheumatism,  67 
condition  in  rheumatic  fever,  66 
damaged,  loss  of  vital  power  due 

to,  51 
fatty  changes  in,  due  to  staphylo- 
coccic inoculation,  58 
injury  to,  in  adults,  due  to  active 

rheumatism,  51 
toxic  action  of  rheumatism  on,  20 
variety  of  pathological  changes 
in,     with     different     morbid 
significance,  50 
See  also  Myocardium 
Heart -wall,  cellular  exudation  in  foci, 
spreading  through    in    rheu- 
matic heart  disease,  65 
changes  in   case   of   diphtheria, 
fatal,      from      cardiac 
failure,  54-56 
in  case  of  fatal  chorea,  58 
in  case  of  rheumatic  peri- 
carditis, 47,  48 


Heart-wall,  fatty  changes  in  case  of 
acute    rheumatism    in, 
56,  57 
throughout,  in  fatal  case 
of  acute  carditis,  52 
microscopic  examination  of  sec- 
tions from,  in  case  of  virulent 
acute  rheumatism,  87 
pericardium  as  support  to,  66 
similarity  of    changes  in  acute 
rheumatism  and  diphtheria,  89 
Heredity,  in  acute  rheumatism,  389 
Herpes  in  acute  rheumatism,  421 
Herringham,  W.    P.,!  association    of 
rheumatoid    arthritis    and     rheu- 
matic fever,  156 
Hicks,  H.  T.,  and  French,  H.  S.,  cases 

of  chorea  gravidarum,  260 
Hill,  L.,  and  Barnard,  H.,  function  of 
pericardium  in  relation  to  heart- 
wall,  66 
Hill,    William,    deep-seated    foci    of 
disease    in     enlarged     tonsils 
removed  from  the  rheumatic, 

273 
tonsils  in  rheumatic  fever,  179 

Hospital  for  Sick  Children,  Great 
Ormond  Street,  analysis  of  fatal 
cases  of  rheumatic  heart  disease 
from,  34-43 

Houses,  damp,  association  of  onset 
of  acute  rheumatism  with,  287, 
292-3,  295-7,  393.  394 

Housing  conditions,  improvements  in 
combating  of  acute  rheumatism 
by,  435 

Hundngton's  chorea,     See  Chorea. 

Hyperpyrexia,  rheumatic.  See  Rheu- 
matism, cerebral 

Infantile   arthritis,    153-4. 
See  also  Arthritis,  infantile 

Infants,  diplococcic  infection  with 
acute  rheumatism  through  pla- 
cental circulation,  389 

Infectious   diseases,   of  other  kinds, 
influence  on  acute  rheumatism, 

393 
specific,  conditions  necessary  to 
produce,  5 
Insanitary  conditions  provocative  of 

acute  rheumatism,  393 
Iritis,  rheumatic,  acute,  209-13 
clinical  position,  209 
experimental    production 
in    rabbits    by    intra- 
venous        inoculation, 
211,  213 


448 


INDEX 


Iritis,  rheumatic,  extreme  rarity,  213 
gonorrhoeal  infection   in, 
210,  211 

Jackson,    J.    Hughlings,    origin    of 
chorea,  237 
pathology  of   chorea,  172,  173, 

174. 253 
Joints,  effusion   about,  in   arthritis, 
human  and  experimental,  142, 

143 

effusion  into,  produced  by  anti- 
toxic sera,  230 
occurrence  of  diplococcus  found 
in  acute  rheumatism  in,  126, 
127 
diplococcus    found    in    mixed 
infection      with     staphylo- 
coccus, 222 
"withering"  of,  in  rheumatoid 
affections,  276 
Josue    and    Salomon,    microscopical 
changes      in      rheumatic      hyper- 
pyrexia, 242 

Keith,  A.,  F.R.S.,  close  relation  of 
cardiac  nerve  and  cardiac  muscle, 
268 
Kelynack,  T.  N.,  relation  of  tonsillar 

inflammation  to  appendicitis,  377 
Kidney,    inflammation,    in    rheuma- 
tism, transitory,  259 
occurrence  of  diplococcus   found 
in  acute  rheumatism  in,   125, 
126 
sclerosis  of,  in  acute  rheumatism, 
407 
Kidneys,     coagulation    necrosis,    in 
rabbits  following  intravenous 
injection   of    diplococci,    114, 
121 
disease  of,  in  mitral  stenosis,  421 
infectivity  of  acute  rheu- 
matism in  relation  to, 

i37»J38 

pathological    changes    in    acute 
rheumatism,  137 
Kirkes,  origin  of  rheumatic  chorea, 
172 
theory  of  choreal  movements, 253 
Koch's  postulates,  demonstration  of 
diplococcus  rheumaticus  fulfilling, 
228,  229,  232 
Kretz,  aetiology  of  appendicitis,  375, 

378,  379,  381 
Kronenberg,  aetiology  of  acute  rheu- 
matism, 97,  98 


Lactic  acid  theory  of  causation  of 

acute  rheumatism,  388 
Laignel-Lavastine,  changes   in  brain 

cells  in  chorea,  255 

Lanz,  experimental  results  connected 

with  suppurative  polyarthritis,  95 

Latham,  P.  W.,  uric  acid  theory  of 

causation  of  acute  rheumatism,  388 

Laurens    and    Macaigne,    rheumatic 

venous  thrombosis,  78 
Lawford,  J.  B.,  gonorrhceal  infection 

in  rheumatic  iritis,  211 
Lees,  D.  B.,  case  of  acute  carditis, 
with  fatty  changes  throughout 
heart  wall,  52 
exciting  cause  of  chorea,  234 
marked    dilatation    of  heart  in 
rheumatism    co-existing  with 
slight  clinical  symptoms,  50 
Letulle     and     Schmidt,     rheumatic 

venous  thrombosis,  78 
Leucocytosis,    in    rheumatic    fever, 

function  of,  179 
Litten,   bacteriology  of  acute  rheu- 
matism, 98 
Liver,  coagulation -necrosis  in  rabbits 
following   intravenous   inocu- 
lation of  diplococci,  in,  112, 
113,  115,  121,  126 
occurrence  of  diplococcus  found 
in  acute  rheumatism  in,  126 
Locality,    influence    on   acute    rheu- 
matism, 393 
Loeffler,    streptococcus    articulorum, 

151 

London,  children  of,  prevalence  of 
acute  rheumatism  among,  393 

Lumbago,  fibrositis  as  form  of,  413 

Lungs  and  pleurae,  occurrence  of 
diplococcus  found  in  acute  rheu- 
matism in,  127 

Lymphoid  tissue  in  appendix,  360 

Macaigne  and  Laurens,  rheumatic 
venous  thrombosis,  78 

Mackenzie,  James,  cardiac  arrhyth- 
mias, 268 

Mackenzie,  Sir  S.,  rheumatic  arth- 
ritis, 151 

Macrae,  rheumatic  iritis,  210 

Malaria,  supposed  affinity  of  acute 
rheumatism  to,  388 

Malkoff,  association  of  chorea  and 
rheumatic  fever,  98,  176 

Mantle,  A.,  microbic  origin  of  rheu- 
matic fever,  94 

Maragliano,  bacteriology  of  rheu- 
matic fever,  95 


INDEX 


449 


Maragliano,  pathology  of  chorea,  176 
Martin,    Sidney,  F.R.S:,  poisons    of 

infective  endocarditis,  204 
Mastitis,  in  acute  rheumatism,  423 
Measles,   followed   by   pneumococcic 
pericarditis,  285 
in    children,  acute   rheumatism 
following,  301 
Meningitis,    cerebro-spinal,  in  case  of 
rheumatism     with     hyperpy- 
rexia, 271 
rheumatic,  acute,  405 
case  of,  239 

post-mortem  results,24i 
diplococcus    from    case    of, 
241,  242 
Menzer,  serum  for  rheumatoid  arth- 
ritis, 161 
Meyer,  Fritz,  diplococcus  from  throat 
in  rheumatic  fever,  180 
experimental       production       of 
chorea,  235 
of  twitching  movements, 

239 

tonsillitis  in  the  rheumatic,  273, 
274 
Micrococci,   streptococcal  group    of, 

difficulties  relating  to,  7 
Micrococcus,  intravenous  inoculation, 
experimental  production  of  rheu- 
matic nodule  by,  2 
Micro-organisms,    causal   agency   of, 
best  means  of  establish- 
ing, 5 
experimental  proof  of,  5 
escape  into  joint  cavity  in  rheu- 
matic arthritis,  vital  process, 
152 
in  urine  of  patients  with  acute 

rheumatism,  95 
invading    body    and    producing 
toxines  circulating  in  system, 
49,  50 
pathogenic,      effects      produced 
experimentally     not     always 
constant,  219 
Milk,    clotting    of,    by     diplococcus 

rheumaticus,  233 
Miller,  Coombs,  and  Kettle,  presence 
of   submiliary   nodules   in   experi- 
mental lesions  produced  by  diplo- 
coccus, 397 
Miller,  R.,  on  chorea,  270 
Mitchell,    J.    K.,    aetiology   of   acute 

rheumatism,  387 
Mitral  valve  and  aorta,  disease  of,  of 
rheumatic  origin,  317-321 
clinical  study,  319 


Mitral  valve,  condition  in  rheumatic 
heart  disease,  34,  38 
from  early  case  of  endocarditis, 
with  severe  chorea,  specimen 
of,  238 
stenosis     of,     association     with 
chorea,  390 
following      acute      rheu- 
matism, mode  of  origin, 
65 
in  adult  female,  of  rheu- 
matic origin,  412 
renal  lesions  in,  421 
Mixed    infection     theory    of    acute 

rheumatism,  100 
Mixed  infections,   clinical  study  of, 

difficult,  221 
Mollet  and  Regaud,  microscopic  in- 
vestigations     of      heart-wall      in 
animals  injected    with  diphtheria 
toxins,  56,  57 
Monarthritis,  occurrence  of,  413 
Monkeys,     effect     of     simultaneous 
injection     of     staphylococcus 
pyogenes    aureus    and    diplo- 
coccus on,  222 
intravenous  inoculation  of   dip- 
lococcus    into,    results,    220, 
221 
production  of  acute  rheumatism 
in,  228,  232 
Motor  system,  predominant  affection 

of,  in  chorea,  256 
Moxon,  W.     See  Wilks,  Sir  S. 
Murray,  G.  A.,  pneumococcus  arth- 
ritis, 157 
Muscles  affected  in  acute  rheumatism, 

400 
Myocardium  and  cardiac  nerve,  close 
relations,  268 
and     pericardium,     concurrent 

changes  in,  49 
changes    in,    relation    to    peri- 
carditis,   clinical  importance, 
65,66 
dilatation    in    rheumatic    heart 

disease,  34,  37 
fatty    changes    in    pericarditis, 

404 
fatty     degeneration     and     des- 
truction   of    muscle -fibres    in 
rabbits  intravenously  injected 
with  diplococcus,  104,  121 
fibrosis   of,   in   rheumatic   heart 

disease,  404 
frequently  first  affected  in  first 
attacks     of     rheumatism     in 
childhood,  60 

29 


450 


INDEX 


Myocardium  hypertrophy  in  rheu- 
matic heart  disease,  34,  37 

importance  in  rheumatic  heart 
disease,  8 

injuries  to,  influencing  prognosis 
of  acute  rheumatism,  427 

lesions  of,  in  rheumatic  carditis, 

4°3.  4°4 
in    rheumatic    heart  dis- 
ease, 416 
pathological   changes   in,    apart 

from  pericarditis,  49 
pathology  of,  63-67 
rheumatic  affection  of,  power  of 

heart  undermined  by,  60 
severe  disease  of,  directly  due  to 
poison  of  acute  rheumatism,  59 
submiliary  nodules  in,  8 
See  also  Heart-muscle 


Naso-pharynx,     attention     to,     in 

rheumatic  children,  434 
Xeck,  rheumatic  venous  thrombosis 
in,  68-78 
and   upper   extremities,   throm- 
bosis of  large  veins  of,  cause 
of   death   in   rheumatic   peri- 
carditis, 48 
Nephritis  in  acute  rheumatism,  3,  421 
persistent    in    acute    rheumatic 
endocarditis,  421 
Xerve-cells,  action  of  bacterial  toxins 
on,  in  chorea,  255,  256 
of  strychnine  on,  256 
of  toxin  of  tetanus  on,  256 
chromatolysis  of,  in  chorea,  254 
Nerves  affected  in  acute  rheumatism, 
400 
cardiac,  and  heart -muscle,  close 
relation  between,  268 
implication  in  myocardial 
lesions,  404 
Nervous  system,  delicate  changes  in, 
resulting     from    acute     rheu- 
matism, 259 
diseases  of,  symptoms  in   acute 

rheumatism,  417 
lesions,  in  rheumatoid  arthritis, 

155 

local  lesions  of,  as  cause  of  chorea, 

237,  238,  239 
manifestation  on  part  of,  in  acute 

rheumatism,  227-43 
morbid  changes  associated  with, 

in  acute  rheumatism,  405 
overstrain    of,    in     relation    to 

chorea,  259 


Netter,     streptococcus     from     case 

resembling  rheumatic  fever,  95 
Neuritis,  in  acute  rheumatism,  405, 

418 
Newman,  Sir  G.,  detection  and  pre- 
vention  of  acute  rheumatism   by 
school  inspection,  434 
Newsholme,    Sir    A.,    association    of 
acute    rheumatism    with    low 
level  of  surface  water,  393 
investigations       of         arthritis, 
161 
Nodules,    rheumatic,    subcutaneous 
396,  399.  4*4 
association  with   heart  dis- 
ease, 414 
depositof  diplococcusin,  8371 
development     of     chorea 
with,  414 
disappearance  of,  259 
distribution    along    tendon 

sheaths,  400 
essential    element    in,    81, 

82 
experimental  production,  2 
by     intravenous     ino- 
culation    of     micro- 
coccus, 2 
frequency  in  fatal  cases  of 
rheumatic   heart   disease, 

34-  4° 
histology,  79-83 
identity     in     early      stage 
when    stained    with    ap- 
pearances     in      endocar- 
ditis     and      pericarditis, 
81 
identity      with      rheumatic 
process     in    endocarditis 
and  pericarditis,  80 
in     acute     rheumatism     in 
children        under        five 
years,    283,    286,    291-3, 
297 
necrosis  of  tissue  in,  83  n. 
occurrence    of     diplococcus 

in,  125 
preparation  of  sections,  80 
purpura  developing  round, 

414 
staining  of,  80 
submiliary,  396,  405 

present  in  experimental 
lesions    produced  by 
diplococcus,  397 
in  myocardium,  8 
Nystagmus,    in    acute    rheumatism, 
418 


INDEX 


451 


Ocular  changes  in  acute  rheumatism, 

420 
(Edema,  acute  pulmonary,  in  severe 
carditis,  420 
pulmonary,  in  acute  rheumatic 
carditis,  407 
Old  age,  acute  rheumatism  in,  391 
Osier's  sign,  swelling  of  finger-tips  in 

malignant  endocarditis,  414 
Osteitis,     rarefying,     of    bone-ends, 

experimental  production,  276 
Osteo-arthritis,  case    of    diplococcus 
isolated  from,  146 
microscopic  and  bacterio- 
logical examination,  1 46 
post-mortem       examina- 
tion, 146 
experimental    production,    145- 

149 
"  guttering  "  of,  276 
in  rabbit  from  inoculation  with 
diplococcus  from  same  disease 
in  human  subject,  146-149 
non-suppurative,     experimental 
production,  275,  276 
Osteomyelitis,  experimental,  363,  364 


Page,  Herbert,  rheumatoid  arthritis, 

case  described,  158 
Pain,  muscular,  in  acute  rheumatism 

in  children,  144 
Paralysis,    symptoms    of,    in    acute 

rheumatism,  418 
Paresis     of     lower     extremities     in 
rabbits   following  intravenous  in- 
jection of  diplococcus,  116,  121,  134 
Parotitis,     severe,     resemblance     of 

venous  thrombosis  in  neck  to,  77 
Pericardial     effusion,    Rotch's    sign 
without,  49 
exudations,     diplococcus     most 

easily  obtained  from,  402 
friction    towards    end    of    fatal 
rheumatic  heart  disease,  34,  40 
Pericarditis    as    terminal    event    in 
acute  rheumatism  in  children 
under  five  years,  284 
cause  of  cardiac  dilatation,  66 
complicating    case    of    virulent 
acute  rheumatism  with  exten- 
sive purpura,  85,  86,  88 
experimental  production  by  local 
injection  of  diplococcus, 
258 
various     infections     may 
cause,  266 
fatal,  with  chorea,  239 


Pericarditis,  identity    of   rheumatic 
nodule     when     stained     with 
appearances  in,  81 
in  rabbits  following  intravenous 
injections  of  diplococcus,  105, 
112,  114,  119,  121 
in  severe  cases  of  acute  rheumatic 
heart  disease,  area  of  cardiac 
dullness  in,  21 
malignant,  207 

pathological    changes    in    myo- 
cardium apart  from,  49 
pneumococcic,  age-incidence,  285 
following  measles,  285 
variety   of    processes   in, 

285 
and  rheumatic,  differences 
in  clinical  course,  284, 
285 
purulent,  and  arthritis  following 
mixed  infection  by  staphylo- 
coccus aureus  and  diplococcus, 
223 
relation  to  changes  in  myocar- 
dium, clinical  importance,  65, 
66 
rheumatic,  acute,  415 

endocarditis      asso- 
ciated with,  415 
detection  of,  415 
fatal  nature  of,  415 
isolation     of     diplo- 
cuccus  from  urine 
during,  135 
age-incidence,  285 
and  pneumococcic,  diffe- 
rences in  clinical  course, 
284,  285 
classification  of  cases,  286 
death  due  to  thrombosis  of 
large  veins  of  neck  and 
upper  extremities,  48 
diagnosis,  easy,  284 
experimental   results   ob- 
tained  from    cases    of, 

133 

fatty  changes  throughout 

heart  in,  66 
following     scarlet    fever, 

285 
identity      of      rheumatic 

nodule  with  process  in, 

80 
increase  in  area  of  cardiac 

dullness  in,  mainly  due 

to  dilatation,  23 
isolation    of,  diplococcus 

from  cases  of,  265 


452 


INDEX 


Pericarditis,   rheumatic,    malignant, 
402 
sequence  of  changes  in,  82 
simple,  401 
variety    of    processes   in, 

285 
with  extreme  dilatation  of 

heart,  case  of,  44-52 
with  fibrosis  of  pericardial 
tissues,  402 
sero  -  fibrinous,      discovery      of 
diplococcus    rheumaticus    in, 
231 
suppurative,   detection  difficult, 

284 
terminal  event  in  case  of  acute 

rheumatism,  59 
tuberculous,  402 
Pericardium,  adhesions,  26,  51 

frequency  in   fatal   cases 
of  acute  dilatation    of 
heart,  36 
adhesions    in    rheumatic    heart 

disease,  34,  36 
and      myocardium      concurrent 

changes  in,  49 
changes  in,  in  case  of  rheumatic 

pericarditis,  47 
clinical     importance     in     heart 

disease,  63 
exudation  into  sac  resulting  from 

rheumatic  poison,  50 
fluid,    in,    in    rheumatic    heart 

disease,  34,  36 
fluid  required  to  distend,  23 
function   as    support   to    heart- 
wall,  66 
inflamed,  post-mortem    appear- 
ances    in     severe     rheumatic 
fever,  65 
paracentesis   of,  cardiac  dilata- 
tion indication  against,  27 
Periostitis,     local,     round     affected 
joints  in  rheumatic  arthritis, 
399 
with  arthritis,  414 
Periphlebitis  and  rheumatic  venous 

thrombosis,  76 
Peritonitis  in  acute  rheumatism,  3 

rare,  422 
Perityphlitis,  association  with  arth- 
ritis, 359-66 
bacillus  coli  in,  364 
in  acute  rheumatism,  360,  363 
in     association     with     arthritis, 

treatment  by  salicylates,  362 
metastatic      suppurations     con- 
nected with,  363,  365 


Perityphlitis,  rheumatic  arthritis  re- 
sembling, 365 

See  also  Appendicitis 
Perivascular  round-cell  infiltration  in 
brain  in  cases  of  chorea,  246,  249, 

251.  253 
Petechiae  in  rheumatic  venous  throm- 
bosis, 78 
Phillips,   S.,   epistaxis  in   rheumatic 
children,  419 
fatal    case    of    infective    endo- 
carditis with  acute  inflamma- 
tion of  ventricle  wall,  52 
Phlebitis,  in  acute  rheumatism,  417 
connection  of  venous  thrombosis 
with,  76 
Pianese,     pathology     of     rheumatic 

chorea,  175 
Piard,    metastatic    suppurations    in 

connection  with  appendicitis,  363 
Placental  circulation,  diplococcic  in- 
fection of  infant  with  acute  rheu- 
matism through,  389 
Pleurae.     See  Lungs  and  pleurae 
Pleurisy,     acute,     in     pneumococcal 
pericarditis,  285 
in  rheumatic  carditis,  406 
plastic,     in     rabbits     following 
intravenous      inoculation      of 
diplococci,  105,  114,  119,  121 
rheumatic,  419 
Plimmer,   H.   G.,  isolation  of  diplo- 
coccus from  rheumatic  nodule,  166 
Pneumococcal    infection     compared 

with  acute  rheumatism,  354 
Pneumococcus,  arthritis  from  infec- 
tion with,  157 
Pneumonia    in    pneumococcal    peri- 
carditis, 285 
in  rabbits  following  intravenous 
inoculation  of  diplococci,  114, 
119,  121 
Polyarthritis    in    rabbits    following 
intravenous  inoculation  of  dip- 
lococcus, 103, 105, 114, 119, 121 
suppurative,     experimental    re- 
sults connected  with,  95 
Poverty  as  cause  of  acute  rheuma- 
tism, 433 
Pregnancy  and  puerperal  state,  in- 
fluence on  rheumatic  infection 
261 
chorea  occurring  in,  fatal  case, 
244,  250 

See  also  under  Chorea 
late  development  of  acute  rheu- 
matism in,  result  on  offspring, 
389 


INDEX 


453 


Prognosis  in  rheumatic  heart  disease, 
importance  of  cardiac  dilata- 
tion in,  27 
in  rheumatic  venous  thrombosis, 

77 
Psoriasis  in  acute  rheumatism,  421 
Puberty,  decrease  of  chorea  after,  418 
Public-school  boys,  healthy  condition 

of  heart  in,  31-33 
Puerperium,   influence  on  course  of 

acute  rheumatism,  423 
Purpura,  extensive,  in  case  of  acute 
virulent  rheumatism,  85,  88 
in  acute  rheumatism,  420 
occurring    round    subcutaneous 
nodules,  414 
Pyaemia,     acute      rheumatism     not 
attenuated  form  of,  224,  232 
and  rheumatic  fever,  analogous 

but  distinct  processes,  157 
arthritis    associated    with    peri- 
typhlitis of  nature  of,  364,  365 
attenuated,    acute     rheumatism 

considered  as,  214,  215 
streptococcus,  cause  of  sup- 
purative arthritis,  case  des- 
cribed, 160 
symptoms  of  predominant,  in 
mixed  infection  with  staphylo- 
coccus aureus  and  diplococcus, 
222 

Rabbits,  chorea  produced  in,  by  intra- 
venous inoculation,  169 
diplococcus    intravenously    in- 
jected into  producing  solitary 
ulcer  in  appendix,  368,  376,383 
experimental  production  of  arth- 
ritis in,  6   158 
from  cases  of   rheumatic 

fever,  141-44,  155.  156 
of  non-suppurative  osteo- 
arthritis in,  275,  276 
experiments   on,   in   demonstra- 
tion of  diplococcus  as  causal 
agent   in    acute    rheumatism, 
103-7,  111-120,  133 
infected,     diplococcus     rheuma- 
ticus  isolated  from  bile  in,  422 
inoculation  of  diplococcus  from 
case  of  rheumatic  meningitis 
into,  results,  241,  242 
inoculation  with  diplococcus  iso- 
lated    from     case     of     osteo- 
arthritis, 147,  149 
intravenous  inoculation  of  diplo- 
coccus into, effects,  103- 
7,   111-115,  117-120 


Rabbits,intra venous  inoculation  from 
rheumatic         fever 
producing        acute 
iritis  in,  211,  212 
of     diplococcus      from 
rheumatic  nodule,  168 
and      local      injections 
of         staphylococcus 
pyogenes  aureus  into, 
results         compared, 
220 
production   of   rheumatic   arth- 
ritis in,  151,  152 
rheumatic  chorea  in,  134, 

235 
resistance     to     inoculation     by 

diplococcus  rheumaticus,  233 
strepto-diplococci  from  enlarged 
tonsil     enucleated    after     re- 
covery from  acute  rheumatism 
inoculated  into,  results,  274 
Raw,    Nathan,   pneumococcus   arth- 
ritis, 157 
Regaud     and     Mollet,     microscopic 
investigation     of     heart-wall      in 
animals  injected   with   diphtheria 
toxins,  56,  57 
Reichardt,  examination  of  brain  in 

cases  of  chorea,  237,  238 
Reproductive  system,  diseases  of,  in 

acute  rheumatism,  423 
Respiration,  organs  of,   diseases  ac- 
companying acute  rheumatism,  419 
Rest,   in   treatment   of   chorea   and 

rheumatism,  27 
Rheumatic  fever,  faulty  term,   270 

See  Rheumatism,  acute 

Rheumatism,  active,  cause  of  death 

in  rheumatic  children,  51 

in   adults   causing  injury 

to  heart-muscle,  51 

acute,  abdominalsymptomsin,422 

aetiology  of, 93- 13 1, 227,387 

chemical        theories, 

388,  394 
theory  of  infection,388 
views  as  to,  99-101 
age-incidence,  391 
agency     of     schools     in 

spread  of,  394 
alteration   of   blood-state 
in,  66 
of     heart-muscle    in 
other  than  fatty,  6  7 
and  chorea,  experimental 
effects    of    diplococcus 
from  fatal  case,  218,  219 
investigations,  170-178 


454 


INDEX 


Rheumatism,  acute,  and  diphtheria, 
effects  of  dilatation  of 
heart  in,  compared,  60 
and  rheumatoid  arthritis, 

156-7 
and  septic  infections,  con- 
nection between,  58 
ante-mortem    thrombosis 

in,  183 
association     with     damp 
houses,    287,    292, 
293.     295-7,     393. 
394 
low   level  of  surface 
water,  393 
bacillus    in     blood    from 
cases  of,  96,  97,  109,  no 
bacteriological   investiga- 
tion, culture  media 
employed,    108 
material  for,  107 
bacteriology,     difficulties 
in,  4 
history,  94-101 
theory,  discussed,  156 
blood-changes  in,  421 
broncho-pneumonia       in, 

407 
campaign      against,      by 
means    of    instructions 
and  lectures,  434 
causal  agent,  diplococcus 

as,  6 
cause  of  malignant  endo- 
carditis, 228,  270 
changes     in     heart-wall, 
similar     to     those     in 
diphtheria,  89 
chorea    associated    with, 
98,  257,  417,  418 
compared     with,     in 
symptoms  and  on- 
set, 258 
first  and  last  symp- 
tom of,  257,  258 
See  also  Chorea,  rheu- 
matic 
climatic  influences,  392 
clinical  features  of,   case 
of  mixed  infection   by 
staphylococcus    aureus 
and  diplococcus  resem- 
bling, 223 
of    scarlatinal    rheu- 
matism,    identical 
with,  300 
compared  with  other  in- 
fections, 354 


Rheumatism,  acute,  condition  of 
cardiac  muscle  in,  66 

considered  as  attenuated 
pyaemia,  214-215,  224 

course  of,  uncertain,  412 

cutaneous  manifestations, 
420 

delicate  changes  in 
nervous  system  result- 
ing from,  259 

dental  caries  and  gingi- 
vitis in,  408 

developing  in  mother  in 
late  pregnancy,  result 
on  offspring,  389 

development  of  gout  in 
later  life  in  subjects  of, 

390 
diagnosis,  425 

by  means  of  medical 
inspection  of  school 
children,  434 
difficulties  in,  424,425 
diarrhoea  in,  422 
dietetic    influences    non- 
existent, 394 
dilatation    of    heart    in, 
marked,     with     slight 
clinical  symptoms, 50,51 
See  also  Heart,  dila- 
tation 
diplococci  at  seat  of  local 
lesions  in,  rapidly  des- 
troyed,   135 
diplococcic     infection     of 
infant  through  placen- 
tal circulation,  389 
diplococcus  of,  95,  97 

constant    in   appear- 
ance in  cases,  post- 
mortem, 263- 264 
as  causal  agent,  165- 
183,  227,  228, 
263,  388,  389 
demonstration 
by         experi- 
ments in  rab- 
bits,   103-7, 
111-120,  133 
demonstration 
from        cases, 
109,  no,  115- 
120, 229 
from     acute     lesion 
intravenously     in- 
jected,    producing 
appendicitis,    367- 
73 


INDEX 


455 


Rheumatism,  acute,  diplococcus  of, 
experimental    inocu- 
lation,     producing 
endocarditis,  215 
from  fatal  case  intra- 
venously      inocu- 
lated  into    rabbit, 
producing       acute 
iritis,  2ii,  212 
intravenous    inocula- 
tion producing 
arthritis,    141-144, 
155,  156 
producing         experi- 
mental     appendi- 
citis, 408 
isolated    in     nodule, 
details    of  investi- 
gations,  166-169 
intravenous   inocula- 
tion of  rabbits,  154 
question         whether 
specific,    123 
diseases    of    reproductive 

system  in,  423 
distinct       and       peculiar 

disease,  6 
endocarditis       associated 

with,  185 
enucleation      of      tonsils, 
after  recovery  from,  274 
epidemic,  392 
epistaxis  in,  419 
fascia?,       muscles,       and 

nerves  affected  in,  400 
fatal   case,    with   chorea, 

235.  236 
fatality  in  children,  59 
fatty    changes    in    heart- 
wall   in   fatal   case   of, 
56,  57 
faulty  term,  270 
fever  in,  422,  423 

as     primary     effect, 

investigations,  180 

following     diphtheria     in 

children,  301 
following  measles  in  child- 
ren, 301 
fresh     manifestations     in 
rheumatic  heart  disease, 

34.  39 
generalised,  course  of,  410 
course     of     virulent 

cases,  412 
history  of   in    child- 
ren, 411 
in  adult,  411 


Rheumatism,     acute    heart    disease 
experimentally         pro- 
duced in,  181- 183 
See  also  Heart  disease 
(rheumatic) 
heredity  in,  389 
hyperpyrexia    in.  See 

Rheumatism,    cerebral 
(below) 
important  part  played  by, 
in  history  of  rheumatic 
heart  disease,  59 
in  children,  9 

affections    of    heart, 

181,  182 
explanation  of  mus- 
cular pains,  144 
myocardium  fre- 

quently      affected 
in  first  attacks,  60 
under  five  years,  281- 
98 
cases  of,  286-98 
diagnosis,  283 
mortality,  283 
pericarditis      as 
terminal  event 
in,  284 
treatment    with 
salicylates, 
290,  296 
in  the  old  or  prematurely 

aged,  391 
incubation  of,  179 
infectivity    of,    1,    2,    61, 
136-138,  435 
in  relation  to  chronic 

arthritis,  137 
to  renal  disease,  137, 
138 
influence   of  locality  on, 

393 

of  malsanitation  on, 

393 

of     other    infectious 

diseases  on,  393 
of     pregnancy     and 
puerperal  state  on 
infection  by,  261 
investigation  of,   difficul- 
ties in,  8 
larynx  rarely  affected  in, 

406 
lesions      of      alimentary 
canal  in,  407,  408 
of  tonsils  in,  406 
local      malignancy,     138, 
206 


456 


INDEX 


Rheumatism,  acute,  local  manifesta- 
tions, symptoms,  413 

local  resistance  in,  135 

micrococcus  of,  8,  9 
site  of,  8 

micro-organisms  in  urine 
from  cases  of,  95 

mitral  and  aortic  disease 
in,  in  relation  to  so- 
called  "  heart-disease," 

317.  3i8 
morbid  anatomy,  396 
morbid  changes  associated 

with  nervous  system  in, 

405 
mucous  colitis  in,  408 

between    attacks   of, 
422 
nervous  manifestations  of, 

227-43,  417 
neuritis  in,  405 
not   an   attenuated   form 

of  pyaemia,  224,  232 
nystagmus  in,  417 
obscure  abdominal  pains 

in,  361 
ocular  changes  in,  420 
onset,  insidious,  207 
origin  of  malignant  endo- 
carditis, 188 
bacteriology,   203-5 
details     of     investi- 
gated   cases,    189- 
201 
histology,  201-203 
origin  of  simple  and  acute 
endocarditis,  blood  cul- 
tures as  test,  disputed 
value  of,  327-9 
origin     of     simple     and 
malignant  endocar- 
ditis.evidence  from 
100    mitral    aortic 
cases,  329-356 
histology,  323-7 
proof       of       theory, 

321-3 
paralytic  symptoms,  418 
pathogenesis  of,  132-5 
pathological    changes    in 
heart  and  pericardium 
in,  401 

See  also  Endocarditis 

Pericarditis 

of  kidney  in,  137 

pericarditis,terminalevent 

in  case  of,  59 
peritonitis  in,  rare,  422 


Rheumatism,     acute,      perityphlitis 
accompanying,  360,  363 
personal  appearance  and 
temperament    in    rela- 
tion to,  391 
phlebitis  in,  417 
pleurisy  in,  406 
poison  of,  causing  exuda- 
tion   into  pericar- 
dial sac,  50 
causing  severe 

changes     in     ven- 
tricle   wall,     little 
demonstrable  mac- 
roscopically,  50 
causing  severe  disease 
of  myocardium,  59 
post-mortem  appearances 
of     endocardium     and 
pericardium  in,  64,  65 
poverty  as  cause  of,  433 
prevalence  among  London 

children,  393 
prevention,  432-5 
previous    history    of,    in 
choreaoccurringinpreg- 
nancy,  260 
process      distinct      from 

pyaemia,  157 
production    in    monkeys, 

228,  232 
prognosis,  425-7 

hygienic    and    social 
conditions  un- 

favourable to,  427 
in    adults    compared 
with  children,  426 
points    for    guidance 
in,  426,  427 
protective  leucocytosis  in, 

179 
purpura  in,  420 
pyogenes  aureus  not  iso 
lated  from  cases 
of,  217,  218 
citreus  in,  95 
rarely  fatal  by  itself,  258 
relation  of  angina  faucium 
to,  96 
of  infective  endocar- 
ditis to,  88 
of  septic   and   rheu- 
matic processes  to, 
206 
of        staphylococcus 
pyogenes      aureus 
to,  214-224 
renal  changes  in,  407,  421 


INDEX 


457 


Rheumatism,    acute,     repeated     re- 
lapses of  chronic  types, 
208 
resistance  to,  great,  258 
respiratory  symptoms,4  la- 
scarred  cardiac  valves  re- 
sulting from,  269 
seasonal  influences,  392 
sex  incidence,  389-90 

greater  in  females  in 
childhood,  390 
simple      and      malignant 
endocarditis,  result  of, 
312 
site  of  infection  in,  95 
specific  nature, 10,  205,313 
staphylococcus  in,  95 
stenosis   of   mitral   valve 
following,      mode       of 
origin,  65 
streptococcus        causing, 
also  cause  of  malig- 
nant endocarditis, 
270 
from      case     resem- 
bling, 95 
streptodiplococcus       iso- 
lated from  case  of, 
271,  272 
inoculated  into  rab- 
bits, 272 
supposed  affinity  to  mala- 
ria, 388 
symptomatology,    410-23 
symptoms,  transitory  na- 
ture of  some,  258,  259 
thyroiditis  in,  420 
tonsillitis    in,    273,    274, 

419 
tonsils   in,    condition    of, 

important,  179 
treatment,  428-32 

by    salicylates,    412, 

429.  43° 
by  serum,  432 
by  vaccines,  431 
curative        measures 
difficult     to     esti- 
mate, 431 
dietetic,  431 
difficulties    in,     428, 

429 
rational  lines  of,  428 
variety    of    lesions    pro- 
duced by,  3 
various  types,  316 
view   that  it  is    not   an 
entity,  282 


Rheumatism,    acute,    virulent,    case 
with  extensive 
purpura,      85, 
88 
complicated    by 
pericarditis, 
85,  86,  88 
microscopic    ex- 
amination    of 
heart-wall,  87 
post-mortem  re- 
sults, 87 
significance  of 
symptoms   in, 
88 
temporary     im- 
provement fol- 
lowed by  death 
from     cardiac 
failure,  86,  87 
with     pericarditis,     fatty 
changes        throughout 
heart  in,  66 
See  also  Arthritis 
cerebral,  241,  242,  405,  418,  422, 

423 
acute  rheumatic  toxaemia 

in, 242 
microscopical  changes  in, 
242 
nature  of,  273 
with     cerebro-spinal 
meningitis,  271 
chronic,  area  of  cardiac  dullness 

in,  23 
development  of,  271 
fresh  manifestations  in  cases  of 
heart   failure    ending   fatally, 
23,  39 
in  children,  acute  dilatation  of 

heart  in,  13-43 
infantile,    origin   and    character 

of,  varying  opinions,  154 
scarlatinal,  299 

arthritis  in,  treatment  by 

salicylates,  300 
clinical  features  identical 
with  acute  rheumatism, 
300 
diplococcus  of,  portal  of 

entry,  300 
in   children,   followed   by 

heart  disease,  302 
isolation  of  streptodiplo- 
coccus   from    case    of, 
300 
prognosis,  311 


458 


INDEX 


Rheumatism,  scarlatinal,   record   of 
cases,  303-10 
relapses  in,  300 
treatment  by  salicylates, 
301 
sore  throat  in,  importance  of,  299 
subacute,  mild,  area  of  cardiac 

dullness  in  first  attacks,  16 
toxic  action  on  heart  muscle,  20 
treatment  by  rest  indicated  by 
cardiac  dilatation,  27 
Rheumatoid  affections,  "withering" 
of  joints  in,  276 
Sec  also  Arthritis,  rheumatoid 
Riva,     bacteriology     of     rheumatic 

fever,  97 
Robinson,    Beverley,    salicylates    in 

perityphlitis,  362 
Rosenthal,  bacillus  of  Achalme,  266 
Rotch's     sign     without     pericardial 
effusion,  49 

of  formic  acid  by  streptococci,  233 
Russell,   J.  S.    Risien,   pathology  of 

rheumatic  chorea,  173 
Ryffel  and  Ainley  Walker,  production 

Sacaze,    site    of   infection   in    acute 

rheumatism,  95 
Sahli,        staphylococcus        pyogenes 

citreus  in  rheumatic  fever,  95 
St.  Mary's  Hospital,  analysis  of  fatal 
cases   of   rheumatic   heart  disease 
from,  34-43 
Salicylates,   administration  in  acute 
rheumatism  of  children  under 
five  years,  290,  296 
in  acute  rheumatism,  429,  430 

estimate    of     value    and 
limitations,  429,  430 
in  arthritis  of  scarlatinal  rheu- 
matism, 300 
in  rheumatic  heart  disease,  27 
in  scarlatinal  rheumatism,  301 
in  treatment  of  perityphlitis  with 
arthritis,  362 
Scarlet  fever  followed  by  rheumatic 
pericarditis,   285 
relation     of     rheumatic     heart 

disease  to,  34,  35 
sore  throat  in,  importance,  299 
streptococcus  isolated  from,  299, 

3°3 

Schiiller,  Max,  bacteriology  of  rheu- 
matoid arthritis,  148 
micro-organisms  in   rheumatoid 
arthritis,  154 

Schmidt     and      Letulle,      rheumatic 

^  venous  thrombosis,  78 


Schneider  and  von  Dungern,  bacterio- 
logy of  rheumatoid  arthritis,  148 
School-children,  medical  inspection  as 
means   of   diagnosis  of 
acute  rheumatism,  434 
in  diagnosis  of  chorea,  434 
Schools,  elementary,  agency  in  spread 

of  acute  rheumatism,  394 
Scleroderma   in    acute    rheumatism, 

421 
Season,  in  relation  to  prevalence  of 

rheumatism,  392 
Septic    infections    and    rheumatism, 

connection  between,  58 
Sequeira,  J.  H.,  pericarditis  as  cause 

of  cardiac  dilatation,  66 
Sera  (antitoxic)  set  free  from  bacteria 
producing  effusion  into  joints,  230 
Serositis,  multiple,  in  rheumatic  peri- 
carditis, 402 
Serum    treatment    of    acute    rheu- 
matism, 432 
Shaw,     Vernon,    local    injection    of 
diplococcus     producing     peri- 
carditis, 258 
production  of  acute  rheumatism 
in  monkeys,  228 
Singer,     aetiology     of     acute     rheu- 
matism, 97 
micro-organisms   in   urine   from 

cases  of  rheumatic  fever,  95 
nature  of  rheumatic  fever,  205 
Sore    throat,    importance    in    rheu- 
matism, 299 
in  scarlet  fever,  299 
in  acute  rheumatism  in  children 
under  five  years,  283,  287,  289, 
293,  296 
Spine,  caries  of,  simulated  by  arth- 
ritis, 413 
Spondylitis,   resulting   from   cervical 

arthritis,  413 
Staphylococci,    experimental    inocu- 
lation   causing    fatty    changes    in 
heart-muscle,  58 
Staphylococcus    and    streptococcus, 
infection   by,  in   causation   of 
acute  rheumatism,  theory  as 
to,  99 
in  rheumatic  fever,  95 
pyogenes  aureus  and  diplococcus 
effect  of  simultaneous  injec- 
tion on  monkey,  222 
mixed  infection,  case  of, 
223 
clinical   features 
resembling  rheu- 
matic fever,  ^23 


INDEX 


459 


Staphylococcus,     pyogenes       aureus 
and  diplococcus, 
purulent  pericar- 
ditis and  arthri- 
tis following,  223 
differentiation    from    diplo- 
coccus, 222 
found    in    blood    in    mixed 
infection  with  diplococcus 
222 
in  urine  from  cases  of  acute 

rheumatism,  95 
inoculation     into     animals 
followed  by  rapid  death, 
222 
intravenous  inoculation  into 

rabbits,  results,  220 
local  injection  into  joints  of 

rabbits,  results,  220 
not  isolated  from   cases  of 
acute    rheumatism,    217, 
218 
points   of   distinction   from 
diplococcus   rheumaticus, 
216,  217 
relation   to   acute   rheuma- 
tism, 214-224 
Staphylococcus   pyogenes  citreus  in 

acute  rheumatism,  95 
Still,  G.  F.,  chorea  in  children,  178 
infantile  arthritis,  153 
mastitis  in  acute  rheumatism, 423 
Still's  syndrome,  case  with  features 

resembling,  289 
Stockman,    R.,   rheumatic   fibrositis, 

401 
Streptococcal    group    of    micrococci, 

difficulties  relating  to,  7 
Streptococci,  differentiation  of,  233 
production   of   formic   acid    by, 

and  in,  233 
saprophytic,  of  alimentary  canal, 
270 
Streptococcus    and    staphylococcus, 
infection   by,  in  causation  of 
acute  rheumatism,  theory  as 
to,  99 
articulorum,  151 
as  cause  of  appendicitis,  380 
cause  of  malignant  endocarditis, 

187 
causing  acute  rheumatism,  also 
cause   of   malignant   endocar- 
ditis, 270 
causing  endocarditis,  267 
from  case  resembling  rheumatic 

fever,  95 
group,  complexity  of,  5 


Streptococcus  in  malignant  endo- 
carditis, no  proof  of  non- 
rheumatic  origin,  328,  329 

infections  due  to,  compared  with 
acute  rheumatism,  354 

isolated  from  scarlet  fever,  299, 

3°3 
pyaemia,  cause  of  multiple  arth- 
ritis, case  described,  160 
pyogenes,  5 

investigations    of,    associa- 
tion   of    rheumatic    fever 
and    malignant    endocar- 
ditis, 199-201 
suggested  identity  of  diplo- 
coccus rheumaticus  with, 
205 
salivarius  or  faecalis,  266 
Strepto-diplococci    from    tonsil   enu- 
cleated    after     recovery 
from   acute   rheumatism, 
274 
inoculated  into  rabbit,  274 
multiplication  in   rheumatic    le- 
sions of  tonsils,  406 
Strepto -diplococcus,     isolated     from 
case  of  acute  rheuma- 
tism, 271,  272 
inoculated  into  rabbits, 
272 
ofscarlatinalrheumatism,3oo 
Strychnine,  action  on  nerve-cells,  256 
Sturges,    O.,    influence   of   fright   on 
chorea,  177 
rheumatic  carditis,  49 
Suppurations,  metastatic,   connected 

with  perityphlitis,  363,  365 
Surface-water,     acute      rheumatism 

associated  with  low  level  of,  393 
Surgical  ailments,  slight,  condition  of 
heart  in   children   suffering  from, 
28-31 
Sutherland,    G.    A.,    perityphlitis   in 

acute  rheumatism,  360 
Synovial      membranes,      connective 
tissues    of,  condition    of   in    rheu- 
matic arthritis,  399 

Tendon   sheaths,    condition    of,   in 
rheumatic  arthritis,  399 
distribution    of    subcutaneous 
nodules  along,  400 
Tenosynovitis,  142 
Tetanus,  toxin  of,  action  on  nerve- 
cells,  256 
Thionin   as   nuclear  stain  for   rheu- 
matic nodules,  80 
stain  for  diplococcus,  122 


460 


INDEX 


Throat,  importance  of  cultures  from, 
in  question  of  causation  of 
acute   rheumatism,    326,   327, 

355 
occurrence  of  diplococcus  found 

in  acute  rheumatism  in,  128 
See  also  Sore  throat,  Tonsillitis, 
Tonsils 
Thrombosis,   ante-mortem,   in   rheu- 
matic fever,  183 
of  large  veins  of  neck  and  upper 
extremities,  cause  of  death  in 
case  of  pericarditis,  48 
rheumatic,     venous,    and    peri- 
phlebitis, 76 
diagnosis,  77 
duration  of,  77 
extensive,   with  severe 
carditis,  cases  of, 
clinical    history, 
68,  70,  72 
post-mortem       re- 
sults, 69,  71,  73, 

74 
mental  apathy  in,  77,78 
origin  of,  76 

question     whether 
primary,  76 
prognosis,  77 
site  of  predilection,  78 
symptoms  accompany- 
ing, 78 
venous,  with   severe    rheumatic 
carditis,  cases  of,  68-78 
Thyroiditis    in     acute    rheumatism, 

420 
Tissues,     demonstration     of     diplo- 
coccus found  in  acute  rheumatism 
in, 124, 135 
Tonsillitis  in  acute  rheumatism,  273, 
274 
in  relation  to  appendicitis,  377, 

379 
preceding  acute  rheumatism,  96 
rheumatic,  419 

streptococcal    follicular,    source 
of      origin      of      appendicitis 
through  blood  stream,  374-7 
See  also  Angina  faucium 
Tonsils   and    appendix    vermiformis, 
structural  analogy,  359,  360 
attention  to,  in  rheumatic  chil- 
dren, 434 
enucleation  after  recovery  from 
acute  rheumatism,  case  of, 


274 
in  rheumatic  children, 
274 


573. 


Tonsils  in  rheumatic  fever,  condition 
of,  important,  179 
portal  of  entry  of  diplococcus  of 
scarlatinal  rheumatism,  300 
Toxaemia,  rheumatic,  cerebral  rheu- 
matism of  nature  of,  242 
Toxins,  circulating  in  system,  origin 
of,  49.  5° 
bacterial,     action      on       nerve- 
cells  in  chorea,  255,  256 
Triboulet,  bacteriology  of  rheumatic 
fever,  97 
micro-organism,    causing    rheu- 
matic fever,  175 
nervous   lesions   in    rheumatoid 

arthritis,  155 
on  suggested  identity  of  septic 

and  rheumatic  processes,  206 
and  Coyon,  researches  on  diplo- 

bacillus,  217 
and    Thiroloix,    diplococcus    in 
aggravated    rheumatic    fever, 

234 

Tricuspid  valve,  condition  in  rheu- 
matic heart  disease,  34,  39 

Trousseau,  angina  faucium  in  rheu- 
matism, 96 

Tuberculosis,  course  of,  compared 
with  acute  rheumatism,  413 

Tuckwell,  H.  M.,  investigation  of 
rheumatic  chorea,  172 

Turner,  Charlewood,  pathology  of 
rheumatic  chorea,  174 


Uric    acid    theory    of    causation    of 

acute  rheumatism,  388 
Urine,     acidity,     in     rabbits    intra- 
venously inoculated  with  dip- 
lococci,  105,  115,  121,  126 
isolation   of    diplococcus    from, 
during  acute   pericarditis,  135 
of  patients  with  acute  rheuma- 
tism, micro-organisms  in,  95 


Vaccines,  in  acute  rheumatism,  431 
Valves,  cardiac,  scarred  through  acute 
rheumatism,  269 
danger  of,  269 
nature    of    vegetations 
on,  269 
Valvular  lesions,  combination  of,  in 

rheumatic  heart  disease,  39 
Valvulitis,    definite,    following   acute 
dilatation  in  first  ^attack 
of  chorea,  area  of  cardiac 
dullness  in,  20 


INDEX 


461 


Valvulitis,  in  severe  cases  of  acute 
rheumatic   heart   disease, 
area    of    cardiac    dullness 
in,  21 
in  rabbits  following  intravenous 
injection  of   diplococcus,  113, 
114,  119,  121 
Ventricle,   fibrosis   of,   in  fatal    case 
of   rheumatic    heart    disease, 
52 
left,  fibrosis  of,  in  case  of,  cardiac 
rheumatism,  48 
specimen  from  case  of  ad- 
vanced    alcoholism,    ex- 
treme    changes     in,     48, 

5i 
Ventricle-wall,  acute  inflammation, 
in  fatal  case  of  infective  endo- 
carditis, 52 
morbid  changes  due  to  rheu- 
matic poison,  severe  but  ma- 
croscopically  little  demon- 
strable, 50 


Walker,  Ainley,  and  Beaton,  isola- 
tion of  diplococcus  from  case 
of  rheumatic  chorea,  235 
and  Rvffel,  production  of  formic 
acid  by  streptococci,  233 
Wall  C,  and  Russell  Andrews,  chorea 
occurring  in  pregnancy,  260 


Warner,  F.,  and  Barlow,  Sir  T.,  iden- 
tity between  rheumatic  process  and 
rheumatic  nodule,  80 
Wassermann,  acute  rheumatism  and 
chorea,  98 
association  of  chorea  and  rheu- 
matic fever,  176 
Water,  see  Surface  Water 
Waugh,  G.,  investigations  upon  the 

tonsils  in  the  rheumatic,  273,  274 
Weber,  F.  Parkes,  infantile  arthritis, 

153 
West,  S.,  myocardial  disease  in  rheu- 
matism, 416 
Westphal,     acute    rheumatism    and 
chorea,  98 
Wassermann,  and  Malkoff,  diplo- 
coccus from  case  of  rheumatic 
pericarditis  and  chorea,  234 
Wilks,    Sir    S.,    connection    between 
rheumatoid  arthritis  and  rheu- 
matic fever,  156 
and  Moxon,  W.,  local  malignancy 
of  acute  rheumatism,  138 
on  rheumatic  arthritis,  142 
Wohlmann,     bacteriology    of    rheu- 
matoid arthritis,  148 
rheumatoid  arthritis  as  a  specific 
disease,  154 

Yeo,  I.  Burney,  perityphlitis    asso- 
ciated with  arthritis,  361 


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